Selectins
and other
mammalian
sialic
acid-binding
lectins
Ajit Varki
University
of California,
San Diego,
La Jolla, California,
USA
Several
recently
discovered
mammalian
cell adhesion
proteins
recognize
and bind to sialic acid-containing
ligands.
Reports
concerning
the molecular
specificities
of these
interactions
have
been
intriguing
but
somewhat
confusing,
partly
because
of pitfalls
in methodology
or interpretation.
Nevertheless,
these
protein-carbohydrate
recognition
phenomena
are
important
in the normal
biology
of blood
cells and in the pathophysiology
of many
diseases.
Current
Opinion
in Cell
Biology
homologous
heen
belie\4 13).gl!~col~iologists
that the speof sugar chains found on mammalian cell suffaces must be involved in specific cell-cell interactions.
Until
recently,
such
recognition was reported mainly he-
It has long
cifc
tjpes
mrimmalian
0ligos;icchxidcS
such as \iruscs, bact4a
xc’
km.
usuall!~
not
for
the
and
nosic~us
agents
toxins. These interactions
and
henc’lit
of
the
m~immali~in
cqin-
Sialic acids are usuall!~ the outermost sugars on mammalian cell surfaces. A% such, they cm slxx3icall~~ or
non-spccifcall\.
repel
ccll<ell
interactions
because
of
their negative charge. In contnlst, scvel-al recentl!~ disco\.ered adhesion proteins spcciticall!~ recognize and hind
to sugar ckns with sialic acids as critical components.
~M:iii)-excellent rr\k\vs h:i\~ been published concerning
the best studied group of sialic acicl-binding lectins. the
selectins, :ind 3r6’ not referred to here because of hibliography size limits. This brief review focuses onI!, upon
sonic’ rec‘ent progress
in this area.
Particulnr
:ittention
is
gi\rcii
to the sial!loligt~s~ic~charicleligancls for the selectins,
the pitfalls in studying them, xncl the multi-step nature of
the cellkcll interactions in Lvhich selectins are in\~ol\~ed.
The rcxler
is referred
to the original literature c.ited for
details ahout these and other r&tccl studies.
Structure
4:257-266
molecules, which are now called the selectins [7**].
The CD22@ lectin [8*,9”] and Factor H of the alternate
complement pathway [ 101 also recognize sialylated ligands, but bear no obvious
homology to one another, nor
to any of the selectins. With the other known sialic acidbinding &tins (the macrophage sialoadhesin [ 11*,1200],
the ganglioside-binding protein [ 13.01 and the placental
lectin [l-i] ), no primary sequence information is yet available. Each stand on their own at present, and hear names
;Lssigned by their discoverers. Some general features of
each of these lectins are summarized in Table 1 and
Fig. 2.
Introduction
twcen
1992,
Selectins and their oligosaccharide
biosynthesis
and structurefunction
relationships
13ecause sialic acids themselves are widespread, the specitic binding of these lectins must involve additional fcJtures of the underlying oligosaccharide structure. In the ’
past two years, there have been I stead). stream of papers
concerning the oligosaccharide ligands recognized by the
selectin farnil!. [ 1546], The declnrati\~e titles of some of
these articles might lead one to believe that final answers
have been found. Howe\?zr, upon further rcdding even an
ficionado
of oligosaccharide structure will admit to bewilderment at the plethora of information and opinions
concerning this issue. For exunple, published opinions
range from the sugcqestion that the simple tetrasaccharide
sialyl-Lewiss (see Fig. 3) is both necessary and sufficient
for biologically nzlevant binding of the E- and P-selectins,
IO those
th:lt indicate
requirements for much more complex recognition motifs. At least some of the confusion
m:1y arise from assuming that the well recognized principles of protein-protein
interactions can be extrapolated
directly to oligos3cch:tride-protein binding.
and nomenclature
The cloning of three indepenclcntl!. cli.scc)verccladhesion
proteins uncovered ;I co~ii~iio~i
scc~~~~~ic~
motif
(Fig.
1)
[ I-5,601. The amino-terminal Icctin-like domains of each
predicted that the!, would recognize specific carhoh!.drates, and this ha.%indeed turned out to he the case.
Given the cotivergent nature of this tield, there arc’ rnan!~
different names for these proteins (Table 1 ). Recently.
a consensus nomenclature ~1s reached for the th rc’c’
Abbreviations
CHO-
Chinwe
harnbter
@
Current
ovary;
I-CAMP
Biology
ligands:
Ltd
Intracellular
ISSN
adheston
0955-0674
molecule
258
Cell regulation
(a)
NH2
LectirKRD)
EGF-like
Complement-binding
Transmembrane
Cytosolic
COOH
6)
Neutrophil
or monocyte
Platelet
Endothelial
cell
Fig. 1.
The selectin
family
of cell adhesion
proteins
showing
the common
sequence
motifs
(a). The cell types
that express
the selectins
under
resting
and/or
stimulated
states are also shown
(b). The general
nature
of the oligosaccharides
known
to be involved
in receptorbinding
are indicated:
4 , sialylated
fucosylated
oligosaccharides
(attached
to ?I; & , sialylated
fucosylated
oligosaccharides
(attached
to
?); I, sialylated
fsulphated?
fucosylated?)
oligosaccharides
(attached
to ?). CRD, carbohydrate-recognition
domain;
ECF, epidermal
growth
factor.
Table 1. The s&z-acid-binding
mammalian
lectms.
Receptor
Isynonyms
Location of
the receptor
L-selectin
(MEL-14 Ag.
gp9OMEL. LAM-l.
Lymphocytes.
neutrophils.
m”““cytes.
eosinophils
LeuB, Ly22,
TQl. DREC.56)
E-selectin
(ELAM-1)
P-selectIn
ICMP-140.
PADCEM. CD621
CD220
(SER. SAR)
H prote,” of
the alternate
complement
pathway
Canglioslde
binding proten
lectin
the llgand
Endothekal cells
k”nstltutlve
or
stimulated
.?Xp~~SSl”~)
or
placental
Neutrophlls.
chronlcally
Inflamed
endothekal cells
monocytes
and
certan lymphocytes
Platelets,
endothekal cells
ktored tn granules)
Neutrophlls.
monocytes and certan
lymphocytes
B cells
Slaloadhestn
Human
Activated
L0cat10n of
Bone marrow
and
Soluble I”
circulating
plasma
Immature
myelold
cells. lymphold
cellsl
‘Non-actwatlng’
cell surfaces
leatures
Proposed
for bIndIng
Lymphocyte
S&I acldls).
fucose reslduesl.
sulfate esters?,
phosphate esters??,
Ion a speafic glycoproteinl)
Slalylated fucosylated
functions
recrrculatlon
extravasation)
lactosamrvz
or glyc”pr”tems?l
Neutrophll adhesion to actwated
endothelwm
Entry of certann
lymphocyte
subsets Into lnllamed
areas
Slalylated lucosylated lact”5amlne
chams. Including
slalyl-Lewis’ and slalyl-Lews”
ilon a specific myeload glycoproteln)
Neutrophil adheston to activated
platelets and endothekum
‘Rolkng of neutrophlls prior to
Smltc aclds on CDJSRO.
mkc aads of CD-75
12.6-lmked 51akc aads
Faalltates ,nteract,ons between
lymphocytes
during response
to antigens?
S~akc aads on 0-lanked
okgosaccharldes
or gangkosldes
SlaaZ-3Calel-3CalNAcl-R
Saalic actds on a varwty
“I
glycoconlugates
(proper blnding
requwes the glycerol-like
ride-than
eXtra”aSatl”n
I
Facllltates r”le of macrophagcs
supporting development of
hematopoelttc
cells?
!Soluble in matrix
Neuronal
cells?
Placental cells?
Saakc aads on neural gangllosldes
Slalic acads on gangllosldes or
glyc”pr”telns
(preference lor
0-acetylated
snlic acids1
I”
Facllltate, contrwed
axes5 of the H
protein to C3b on cell surfaces.
prevent,ng ampllRcatl”n
of s~akc acndsl)
Membrane-associated
I” myelm sheaths?
Into
lymph nodes
Neutrophll ‘rollmg’ prior to
chams mcludmg
s~alyl-LWISX and s~alyl-Lews~
(on glycokplds
Certam T cells.
actwated B cells
lymph node
macrophages
Structural
necessary
Organlzatlon
of myelrlll
Unknown
Selectins
Fig. 2. Mammalian
ligands are shown.
sialic acid-binding
proteins
other than
Details of the minimal
ligand structure
lessons
past
from
the
about
the selectins.
recognized
lectins
Past studies of plant and animal lectins have shown
some distinctive features of protein-oligosaccharide
interactions. First, defining the binding specificity of a lectin
in terms of the simplest monosaccharide or oligosaccharide recognized is useful (e.g. M6P receptors recognize
mannose-6-phosphate).
However, the biologically relevant ligands tend to be much more complex (mannose-6phosphate has an association constant in the micromolar
range for the M6P receptors). Thus, the identification of
sialylated fucosylated lactosaminoglycans (such as sialylLewisS) as ligands for the selectins may represent only a
first step in the right direction.
Second, multivalency is the rule rather than the exception
in lectin binding and can involve multiple branches of
a single oligosaccharide, multiple oligosaccharides on a
single macromolecule, or multiple oligosaccharides on
multiple macromolecules. This gives rise to a spectrum
of possible interactions, ranging from trivial to very highaffinity binding. Which of these is biologically relevant
may well depend upon the situation under consideration.
and
other
mammalian
sialic
The cell types or tissues known
for each case are not shown.
H,
acid-binding
lectins
to carry the
sialic acid.
receptors
Varki
and
the
Third, the precise conditions used to study the interactions (time, temperature, shear force, etc.) can greatly
affect lectin-binding, and hence the interpretation of its
significance.
apparently unrelated oligosaccharides can inhibit
the same lectin-like interactions because some aspects of
their structure in free solution mimic one another.
Fourth,
What
do
saccharide
inhibition
studies
tell
us?
Although inhibition studies with deftned oligosaccharides
are very useful, they must be interpreted with caution.
The plethora of saccharides that inhibit L-selectin binding
are a case in point. On the one hand, they do reinforce
the notion that carbohydrates are critical in the interaction. On the other hand, if interpreted liberally, they
could
lead to the conclusion that the natural ligand must
contain fucose-3sulfate, mannose-6-phosphate, a-linked
sialic acids and ceramide-linked galactose-3sulfate. Some
of these may well turn out to be present in the native lig-
259
260
Cell
regulation
.
Binding
to:
CEPLS
+--me
Calpl~4CicNAc~l
crype
2 Precursor)
Si~~6C;alel~4CIcNAcet-R~-
-R
Lewis’
+Calj31+4ClcNAc~l-R
3
t
?
1
FZC
v
-!Siaa2~3Gal~l~4GlcNAc~l-R~-
-+++?
?
Siaa2-+3GalP1~4GlcNAc~l
-R
:
1
F:c
swylw
SiaaZ-3Ga@l
-+++?
-3Gl;NAcfll-R+-
?
{~~Gal~l~3Gl~~~~~~
Siaa2~3Gal~l~3GlcNAc~l-R
t
1
1
F:c
.
-
-
? +
Siaa2~3Gal~l~3GalNAcl-R
+-
GalfilA3GalNAcl
-R
-I=\
Siaa2
46GalNAcl
-R
F’c
Fig. 3. Some sialyl-oligosaccharides
recognized
by the sialic acid-binding
proteins.
The minimal
terminal
sequences
known
to be recognized by various
sialic-acid
binding
mammalian
lectins
are shown
In the boxed
area. C. CD228;
E. E-selectin;
L, L-selectin;
P, P-selectln;
S, sialoadhesin.
The immediate
biosynthetic
precursor
structures
of each are Indicated.
along
with a few oi the possible
alternative
biosynthetic
pathways.
Fuc, fucose;
Gal, galactose;
CalNAc,
N-acetylgalactosamlne;
ClcNAC.
N-acetylglucosamine;
R. core sugar chain,
Sia. sialic acid.
The exquisite specificities of monoclonal antibodies have
been used successfully to study the importance of particular regions of polypeptides in cell-cell interactions.
However, this approach is less useful with anti-carbohydrate antibodies. Most such antibodies are &MS, and b>
sheer size are likely to block much more than just their
cognate ligands. Further, the widespread distribution of
the cognate oligosaccharide antigens on surface proteins
and lipids can result in a very high surface density of the
applied antibody. Thus, controls that result in a similar
surface density of class-matched antibodies are required.
ever. it is somewhat ditficult to use data from such esperiments to predict the precise nature of the biologicall!- rele\ant l&and. This is hecause unnaturall!~ high
densities of the receptor and, or ligand are likely to be
present. Thus, mutant or transfected Chinese hamster
ova? (CHO) cells expressing high levels of sialylated
fucoylated lactos:uninogl!,cans bind quite well to plastic
surfaces coated with the I+ielectin, and also to COS cells
over-expressing this receptor. This whole-cell binding is
indistinguishable from that of neutrophils or HL-60 cells
carging the biologically releEmt natural ligand for the
selectin. Howe\,er, direct binding studies indicate that the
CHO cells simply have very high levels of low-:&%5
non-saturable binding sites, whereas the my&id cells
have high-al%@, saturable binding sites. In fact, the latter
account for only a very small portion of the sialylated
oligosaccharides on the myeloid cell surface. and ma). be
present on a single glycoprotein (Moore KL, Stulw. NL,
Smith DL, Cummings KC, Varki A. McEver Rp: NIoocll991
[abstract], 78:108a). The challenge then is to discover the
precise structure of such high-affiniv ligand(s) for each
selectin.
High
Inhibition
and, but others are probably acting as structural mimics
in the inhibition experiments. However, recent evidence
does suggest that sulfated oligosaccharides may be recognized by selectins with a calcium-independent binding
site, separate from that which recognizes the sialylated
ligands [47,48*]. If so, exploring the natural ligands for
these receptors will be even more complicated.
Difficulties
densities
in
using
can
antibodies
obscure
against
ligand
carbohydrates
specificity
Purified receptors or ligands in immobilized form (e.g.
on plastic surfaces) have allowed identification of man)
biologically important binding reactions. Likewise, transient transfection experiments can provide high levels of
specific receptors expressed on COS cells. These two
approaches have even been elegantly combined by overlaying COS cells overexpressing a selectin onto purified
glycolipids on thin-layer chromatography plates. How-
studies
with
glycolipids
Inhibition of lectin-binding by pure glycolipids hzs also
been used to define the nature of the cognate oligosaccharide ligands. Dramatic differences in the inhibitory c:lpaciv of various structures are seen, and apparent inhibition constants in the nanomolar range suggest that
certain sugar sequences are both nccessar)’ and suficient
for biologically relevant binding. However, pure sialylated
glycolipids (gangliosides ) ha\,e ver)l low critical micellar
Selectins
concentrations and hence usually exist as micelles. This
results in a high-density, functionally multivalent presentation of the oligosaccharide ligand. In the natural situation, however, gangliosides usually represent only a small
percentage of the total cell-surface lipid, and thus could
not easily present themselves at such high densities. On
the other hand, it must be admitted that domain formation or clustering of gangliosides could occur in specialized areas of a cell surface.
Using
glycosidases
on
intact
cells
Treating cells with glycosidases is a useful way to explore the specificities of lectin-binding. However, many
commercially available glycosidases contain traces of proteases and other glycosidases. This is not usually of concern when they are used to sequence pure oligosaccharides, because small amounts can be used for short periods of time and the consequences can be determined directly by chemical analysis. However, extensively removing a specific type of sugar from a complex cell-surface
‘glycocalyx’ is virtually impossible, even using large quantities of enzymes and/or extendecl incubation periods.
This is like trying to eradicate a specific type of plant from
the Amazon jungle using a squadron of helicopters with
flame throwers. The mission is likely to be only partially
successful and some collateral damage can be expected.
Additionally, certain sialidase preparations (e.g. the a2-3specific sialidase from New Castle Disease virus) consist
of entire virions, and steric hindrance to enzyme action
on cell surfaces is of even more concern. Furthermore,
such preparations also have a hemagglutinating activity,
which could result in spurious cell-cell adhesion. In spite
of these probltihis’, siali&ses have played a useful role in
exploring the binding of most of the lectins discussed
here. One wry to improve specificity is to carry out a
control experiment in which a specific sialidase inhibitor
is added. However, this requires careful titration of the
concentrations of the enzyme and the inhibitor.
Generating
specificity
from
common
structures
Although sialylated, fucosylated lactosaminoglycans are
found in alx~~d~~~e on the cells recognized by the selectins [ 49**,50*], they are also found on many other cell
types and secreted proteins. How can such a relatively
common structural motif be used to make specific ligands for the selectins? One explanation is that physical
barriers limit their availability; e.g. the oligosaccharides
found on many epithelial glycoproteins would not be encountered by the intra-vascularly expressed selectins, except in pathological circumstances such as cancer. However, it is more likely that specilicity might be provided
by delined spacing and/or presentations of the relevant
oligosaccharides on specific protein carriers. It is also
possible that portions of a relevant glycoprotein carrier
might serve as direct contact points for enhancing the
specificity of binding. Finally, it is possible that a corn
mon oligosaccharide structure could become more specialized (e.g. by sulfation. or modilications of the sialic
acids ).
and
Sialic
other
mammalian
acids:
a diverse
sialic
acid-binding
lectins
Varki
family
Most studies equate ‘sialic acid’ with the common sugar
N-acetyl-neuraminic acid. The sialic acids are actually a
diverse family of acidic sugars, which have in common
only a nine-carbon backbone and an a-linkage. This diversity is largely ignored in studies of sialyloligosaccharides, primarily for technical reasons. However, there are
clear examples where specific types of the sialic acids
can mediate specific binding phenomena (see [51] for
review>. Thus, it is possible that the binding specificities
of some of these sialic-binding proteins could be determined, modulated or diversified by changes in the type
of sialic acid iI the natural ligands.
Studies
vivo
of cell-cell
interactions
in vitro
and in
Many studies of cell-cell interactions involving the selectins have been published recently [ 52-851 and cannot
be described individually here. However, some general
principles that emerge are discussed below.
Measuring
adhesion:
the
importance
of motion
Until recently, most assays for adhesion were performed
in static systems. However, blood cells normally experience substantial shear forces in the vasculature. Under
such conditions, the differences in on-off rates between
lectin-like interactions and protein-protein
interactions
may be particularly important. Thus, although integrinmediated adhesion plays a prominent role in static assays
(particularly at physiological temperatures and even more
so if the cells have been activated), the contributions
of lectins are harder to detect under such conditions.
Upon introducing a shear force (e.g. rocking, flow conditions), the multiple contributions of different adhesion
molecules can be detected more specifically. However,
in any such studies, interference with any one of the involved systems can result in complete loss of adhesion.
Consider a rock-climber on a sheer cliff face, buffeted by
strong winds. Each and every one of the climber’s holds
are critical and detachment of even one would be fatal.
Multiple
steps
and
combinatorial
possibilities
Although in llitt-o assays can be engineered to emphasize the contributions of single ligdnd-receptor pairs, the
natural process by which a leukocyte passes through
an endothelial barrier involves many interactive mechanisms. Current published data suggest that multiple sequential steps occur in leucocyte-endothelium
interactions. Different combinations of these steps could account for the generation of specificity using a limited
set of receptor-ligand and cytokine-receptor pairs. For
example, current literature suggests that the following
steps occllr in acute neutrophil extravasation from the
circulation: (i) activation of *he endothelium and/or neutrophil by an exogenous agent; (ii) rapid expression of
261
262
Cell
regulation
.
the P-selectin on the activated endothelial surface; (iii)
expression of an as yet unknown L-selectin ligand on
the activated endothelium; (iv) an unexplained improvement in the binding affinity of the neutrophil L-selectin;
(v) ‘rolling’ of the neutrophil on the endothelium, mediated by either or both of these selectin interactions; (vi)
shedding of the L-selectin from the neutrophil surface;
(vii) delivery of ‘juxtacrine’ signals between the endothelium and the neutrophil (e.g. platelet-activating factor,
interleukin8); (viii) an unexplained improvement in the
binding affinity of the neutrophil integrins for endothelial
intracellular adhesion molecule (I-CAM); (ix) arrest of
the neutrophil on the endothelium; (x) recruitment of
more integrin receptors to the neutrophil cell surface;
(xi) new synthesis of E-selectin and I-CAM molecules
by the endothelium, enhancing the binding of the neutrophils; and (xii) neutrophil spreading and invasion.
Which of these events ac&ally occur in a given situation,
in precisely what order, and how much they each contribute probably depends upon the inciting stimulus, the
specific cell types involved and the overall setting.
Neutrophil
extravasation
can
be
harmful
In the normal animal, neutrophils constantly exit the circulation and destroy invading microorganisms. In active
infections this process is accelerated and serves a vital
role in the survival of the host. However, in many pathological states (including some induced by man-made manipulations), this process proceeds unchecked, resulting in unwanted tissue injury by the neutrophil. Because
the selectins appear to be involved at an early phase
of this extravasation, the possibility of blocking or attenuating these pathological processes has raised great
excitement among biologists, synthetic chemists, pathologists, clinicians, biotechnologists and investors. In this
regard, recent published studies in animal systems have
been very promising [ 54*,66*,80**,81], providing strong
grounds for such optimism.
Conclusions
and future
prospects
The excitement in the field of selectins is pdpable, and
with numerous academic laboratories and biotechnoloa
companies jumping into the fray, progress will continue
to be fast and furious. In fact, this review will no longer
be ‘current’ by the time it is published. However, as with
uncontrolled and excessively rapid DNA replication, the
error rate is likely to continue to be high. Fortunately,
the inevitable self-correcting mechanisms of science will
come into play, and when the dust settles, the major issues should be resolved. Action in the following areas is
likely to continue.
From the biologists point of view, it seems critical to first
elucidate the exact nature of the natural &and for these
receptors. However, biotechnology companies will continue to generate synthetic ligands for the selectins, which
could be used as soluble inhibitors in the whole ani-
mal. From the strictly pharmacotherapeutic point of view,
what may be sufficient is a compound with favourable
pharmacology that will effectively inhibit the interaction.
How closely such a compound is related to the natural
&and is of interest, but is not immediately critical.
The role of the selectins in leucocyte t&Xc is clear in
acute inflammatory situations, and evidence for their role
in chronic intlammator)~ states has been forthcoming. Because the half-life of some cells (e.g. the neutrophil) is
very short even under normal circumstances, the question arises of whether the same mechanisms are operational in regulating normal neutrophil traffic.
The mechanisms for temporal and spatial regulation of
expression of these receptors await further exploration.
In the case of their cognate oligosaccharide ligands, the
regulation of the relevant glyco.syltransferases and the
protein sctiolds that carry the sugars requires investigation.
Because the cytoplasmic tails of the selectin molecules
are highly conserved, they could be involved in delivering
signals upon binding. If the selectin lig‘ands indeed turn
out to be carried by specific proteins, it is also possible
that these molecules deliver signals to the cells carrying
them.
With the limited number of receptor-ligands for blood
cells and endothelia described so far, it is hard to explain the extent of specificity seen in leucocyte homing to specific tissues, under specific conditions. Various
combinatorial possibilities between the multiple steps in
leucocyte-endothelium
interaction could be responsible
for generating a range of distinct interaction sets. This
may explain the many different types of leucocyte homing
that can occur, using a few ligand-receptor pairs, and a
few juxtacrine signals. Exploration of such combinatorial
possibilities is likely to continue.
Of the receptors described in this review, some were
initially identified as lectins, primarily on the basis of their
amino acid sequence. It is safe to predict that more such
‘reverse glycobiology [86] wiill occur, and that the family
of sialic acid-binding proteins will expand. If this happens, defining the fine specificities of the sialylotigosaccharide ligands for each receptor will become even more
important.
References
PJperS
\icw.
.
..
and recommended
of particular
interest,
puhlishcul
have been highlighted
as:
of special interest
of outstanding
interest
within
reading
the annual
period
c,f re-
1.
KI~HIh!OTo
TK. Jtl’rtl~
MA. B~TCIIEH
EC: Identification
of
a Human
Peripheral
Lymph
Node
Homing
Receptor:
a
Rapidly
Down-regulated
Adhesion
Molecule.
I’tw Ncrtl Acud
Sci 1’ 5 A 1990, 87:22-1+224X.
2.
ML, KINGSMOKE SF, JOItNSt’ON
GI. SII:C;I~I~~AN Ml-l. I.ii
13O.t’ MM, tJihlON5 KS. HoKA NS, HOWARD TA. WI:I~S,\IAN II,
MCEVE:H RP. %I.lxN
MF: Genomic
Organization
of t;le Selectin
Family of Leukocyte
Adhesion
Molecules
on Human
and Mouse
Chromosome
1. ./ Exp &~I 1990. 172:26.%272.
\xi.tnON
Selectins
3.
COLLINS T. W~uuhis
A, JOtlNSTON
Gl. KIM J. EIX>Y R, SHOU%
T, GlhlllRONI:
MA JH. Blivllncy~i~
MP: Structure
and Chromosomal
Location
of the Gene for EndotheliaI-Leukocyte
Adhesion
Molecule
1. J Hid Chetn 1991. 266:ZrGG2473.
4.
JOIINSTON GI. Bl.lss GA NEW’hlAN PJ, McEvtx
RP: Structure
of
the Human
Gene Encoding
Granule
Membrane
Protein-140,
a Member
of the Selectin
Family of Adhesion
Receptors
for
Leukocytes.
J Hit)/ cl~em 1990. 265:21381-21385.
5.
I.OtW RR, Ctil-Ross0
G. kONI: DR. Kosh MD, BIXtEK S, Nli~htAN
BM. I.lUIOW’SliyJ
S. BliNJAhllN CD, DCM’GA\
IG. GOlitZ
SE,
I Itih>loh’ C. Ct IOW’ El’. Expression
and Functional
Characterization of a Soluble Form of EndotheliaI-Leukocyte
Adhesion
Molecule
I. ./ /nfmu,ro/
1991. 147: 124-129.
6.
.
An
one
two
rhis
ANIX%ON
DC, ItiKy
L. Bl’TcllliH
EC, Mn’,~S\s,\t& M. GALlATIN
M. SCOIJAI’ R. ROSt:N 5. ShllTt I CW. KlslllhlO-l-0
K, HA~ARI)
D: Peripheral
Lymph
Node
Homing
Receptor
(LECAM-I).
Immfrml
?ixlu,~ 1991, 12:216.
attempt
is made to reach a consc’nsus
regarding
nomencla[ure
of
of the Icytins. The acrc,n)m
LECAM ih then exrcnded
to the orher
homologous
proteins.
namely. LECAM 2 and LECAM3.
tIo\vever.
h;w now been abandoncul
in favour of ‘.selectins’ (see [ 7.0 ) ).
BI~~IIA~~I’A
M. Br’x:tw~
E. F’w
I~. GAI.I,\‘I~s
M. Glwtusk
M, ILUIIAY J. Kl>tllhlw’o
K, I,\%~
1.. IMCEVER R. P,u’l.\os
J.
1;~ ..I/.: Selectins:
a Family of Adhesion
Receptors.
Cell 1991,
67233.
A ( hopefully)
linal agreement
regardmg
nomenclature
for the three
homologous
adhesion
prc)reins
This 11’:~s achieved
primarily
through
the elli)rts of Richard I Dynes of MIT, who then modestly
refused 1‘1 pur
his name on the tinal letter.
and
SI’AhIENKO\~l(: I. AVllithl
I I(:. I)li(;~;liKI)Al.
A. Bl.OhllIOt+
IHK.
Shll%w)
EB. Fl’NlXHl’I)
5, The B CeU Antigen
CD75
is a
Cell Surface
Sialyltransferase.
./ /;17> ,I/& 1990. 172:6-1~~3.
~lsprcssion
cloning of CD75 )iclcls ;I cl>NA for :I prr\iously
sequenced
I;~cr~~saminc-sp~citic
z2 6 si:llylrr;lnsfcr;lse.
The antigen could be either
the tr.tnsfcr.ac
irsclf. or a specilic
z? 6 linked sial~loligosacchariJr
scqucncc’ gcner.Wd
I,!, it.
Slx>ll<NK;c,Vlc I. SCROI D. ARI’I:FO A, Sy MS, A,YlXRsON T. The
B Lymphocyte
Adhesion
Molecule
CD22
Interacts
with
Leukocyte
Common
Antigen
CD45RO
on T Cells and ~2-6
Wyltransferase.
CD75.
on B Cells. Cell 1991, 66:1133-l
l-14.
I)emonstratlon
of the dirccr
binding
of a soluble
form of CD22g io
I!mphoc~W
su1~scls expressing
specilic
cognate
ligancls. In each case.
binding
is completely
ahc&hed
by sialiclasc.
in&caring
a critical
role
for slalic acid in rccognitlon.
Direct exploration
of the nalure of lhr
cogn;W
ligancls i> no\v fezsiblc.
l‘l
15.
.
I I.
.
hll:RI S. I’~\N(;I%I‘RN
and Nonactivators
ment: Regulation
on Factor
H. I’)TK’
hlK: Discrimination
Between
Activators
of the Alternative
Pathway
of CompleVia a Sialic Acid/Polyanion
Binding
Site
:Wct/ :li~r~/ Sir 1 ‘.S..I 1990. 87:39X2-3986.
CH(x.K(I-H PK. WEHI( %. GOIUX)X 5. BhlN’fos
DF. Llhrastructural
LocaIization
of a Macrophage-restricted
SiaIic Acid
Binding Hemaggtutinin.
SER. in Macrophage-Hematopoietic
Cell
Clusters.
/~/otw/ 1990, 76: I I.3 I I 13X.
sialic
acid-bindine
Varki
lectins
AHhlED H. GMIIIS H.J: Purification
and Properties
Independent
SiaUc Acid-binding
Lectin
from
centa and Preferential
AlXnity
to O-Acetylsialic
Clxm
1989. 26&l&73-18678.
263
it likely
and/or
of a Ca*+Human
PlaAcids. / Biol
NICOLAOI~ KC, CALWEID
TJ. KATAOKA H, SIYUNIDES
Synthesis
of the Tumor-associated
vex
Family
sphingolipids.
J Am C&em Sot 1990, 112:3693-3695.
One of several efforts
hy synthetic
chemists
to produce
quantities
of the minimum
ligands for the selectins.
Nk Total
of Glycosubstantial
16.
Silicet,%w
MH. CHENC IC, Wmihtm
IL, W.wamD
EK: The
Mouse Lymph
Node Homing
Receptor
is Identical
with the
Lymphocyte
CeII Surface
Marker
Ly-22:
Role of the EGF
Domain
in EndotheUaI
Binding.
Cell 1990, 61:611-622.
17
WA’MN
SR. lxw 1’, FENNIE C. GEOFFROS JS, ROSEN SD, Lvw
1A: A Homing
Receptor-IgG
Chimera
as a Probe for Adhesive Ligands
of Lymph
Node
High EndotheIiaI
Venules.
J
Cell Niol 1990, 110:2221-2229.
IX.
lht.\l Y. Tm’I; DD. SI%Ct% MS. ROSEN SD: Direct
Demonstration
of the Lectin
Activity
of gp9OMEL,
a Lymphocyte
Homing
Receptor.
.I Cell Rio/ 1990. I 11:1225-1232.
19.
LIEN
E. P,u,uwc~
T. SAJ~~RS. Gttmtm
GE, WAGNER DD, FURIE
BC, FI:RIE B: PADGEM-dependent
Adhesion
of Platelets
to
Monocytes
and NeutrophUs
is Mediated
by a Lineage-specific Carbohydrate,
LNF III (CDIS).
Cell 1990, 63:167474.
20.
..
Whl% G, AHI:FFO A. KOLANIIS W. BRILACQLIA M. SEED B: Recognition
by ELAM-1 of the SiaIyl-LeX
Determinant
on Myeloid
and Tumor
Cells. Scietzce 1990, 250:1132-1135.
One of a cl&sic group of papers appearing
in late 199il that demonstratcvl the rote of rhe sialyl-lzwisS
motif in recognition
by the Eselectin
(FlAXI).
21.
9
..
IO.
mammalian
within the central and periphenl
nervous
system. This makes
that the receptor
plays some specific role in neural development
tissue organization.
..
x
.
other
Tll<nlti~-tx
M. S~‘It3XER
SJ. ISHIHARA
IM, MOREIAND
SCI~~~I~~~;R~~~EH IH. HiKrzeR
P. BKWDEY
UK: Carbohydrate
Ligands
for EndotheliaI-Leukocyte
Adhesion
Molecule
Pros ,Vd Acutl Sci I S .1 1991, BB:lI3%1
142.
M.
I.
22.
COKR,~. I, SI%EH MS. MA(:IIER BA. ROSES SD: Requirement
for
SiaIic Acid on Neutrophils
in a GMP-140
(PADGEM)
Mediated Adhesive
Interaction
with Activated
Platelets.
Bicdxnz
Ni@q:v
Km Cor?rmrr~~ 1990, 172: 1319-1356.
3.
GOEU. SE. IH~woir: C. Gow
D. Gwwr~s
B, TV!
R. NEU(‘U~N
1~. Citi-Rosw
G. l*?t%t% K: ELFI’: a Gene
that Directs
the
Expression
of an EIAM-I
Ligand.
Cell 1990, 63:134+1356.
I*)w
JB. Smoixi.~s
LV. NAIR RP. LWES
KD, BEmt:sn
TL
MAWS KM. ELAM-l-dependent
CeU Adhesion
to Vascular
Endothelium
Determined
by a Transfected
Human
Fucosyltransferase
cDNA.
C& 1990, 63~1~5-+8~.
Another
of a classic grcjup of papers that lirst reported
a role for the
sialylared
fucos+WtyI
oligosaccharides
in recognition
by the E-selectin
(Elfi
I ).
24.
..
PI~II.IJPS hll.. Nilnwux
E. GAETA FCA, PEREZ M. SINCHAI. AK,
I IAKOAIOKI 5. PA’I.~OS JC: ELAM-1
Mediates
CeU Adhesion
by
Recognition
of a Carbohydrate
Ligand.
SiaIyl-LeX.
Scieplce
1990, 25O:ll.WI
132.
1’et ano~hrtr of a ~I:LSSIC group of papers ihat lirst reported
a role for
rhc sialyl-ltiv.is”
motif in rccogniWn
by the E-selectin
(ELAM.1 I.
25
..
12.
..
C~octxtt
PK. Kli~.\t 5. Ikl{ols
C. MA~IN
B. hlcWi~~i\.\!
A\.
51 IOI-I.ON DM. PA~I.~oF; JC. C~~)KIX)N S: Purification
and Prop.
erties
of SiaIoadhesin.
a SiaIic Acid-binding
Receptor
of
Murine
Tissue
Macrophagcs.
fi\//<o./
1991. 10:1661-1669.
A c.areful study tlsing state of the art tcchniclucb
10 clenionstr.ltc
the
minimal
structural
requirenicn1.4
for specitic
rccognlrion
of 3 sial!,l
oli#osa~chancle
by Ihe mscrophage
rcccptor.
The sequence
in qucs
tic )n (Sia& 3GalP I -3GaINAc)
is common
both
to serinc thrconinc
O-linked
oliKosacchsride~
and to certain gangliosides.
1.3.
..
Tiiixck?‘ii~i hl, SW~K I11l.b P. SLIIN.QW KL A Membrane
Receptor for Gangliosides
is Associated
with
Central
Nervous
System
Myelin. ,/ Hid cjrxw
1900. 265: 1 I99(t I 19?I9.
A foUo\v up to euller studies hy the same group. The ganglioside
rc’
cclxor
shows a remporally
and spatially defined patlem of expression
E
26.
..
THIW DD. SIN~XR MS, L\WY IA. KO~EX SD: Requirement
for
SiaIic Acid on the EndotheliaI
Ligand
of a Lymphocyte
Homing
Receptor.
./ Cell Rid 1990, I1 1:2757-276+
Closes the loop on the seminal ohsenation
made hy the same group
in 1985, thar sialic acid must he important
in the recognition
of high
cndothelial
vrnules
of lymph nodes bv circulating
Iymphoc>Tes.
In this
instance, the requirement
for sialic acid is demonstrated
directly
using
;I recombinant
soluble
Form of the Lselectin.
27
.
MOORE KL, V.~I
A, McE\w
RI’: GMP-140
Binds to
coprotein
Receptor
on Human
Neutrophils:
Evidence
Lectin-like
Interaction.
.I Cell Rid 1991, I12:491199.
a Gly
for a
264
Cell regulation
Direct evidence
for a small number
of high.;finiv
binding sites for the
P.selectin
(GMP-140)
on myeloid cells. This study also shows that sialic
acid is required
for binding and that the Lewiss motif (see [ 191 ) cannot
itself be sufficient
for recognition.
28.
KA~~EYA&M A, ISHIIIA H, KISO M. H;\SEGAU’A A Total
.
of Sialyl Lewis X. G&d?)&
Ke\‘ 1991, 209:cl~i.
Another
example of efforts hy s)nthetic
chemists
to produce
mum ligands for the selectins.
Synthesis
the min-
BERG El Rou~~solu
MK, wvsso~
0. Btxttett
EC. MASGSASI
JL: A Carbohydrate
Domain
Common
to Both
SiaIyl Lea
and Sialyl
LI&X is Recognized
by the
Endothelial
Cell
Leukocyte
Adhesion
Molecule
ELAM-I.
.I Hiol cl,c~~?~ 1991,
266:1.@6+1-r872.
A surprising
and counter.intuitive
ohscnxion
that si;tIyl-lrwisl
(;m ISOmer of sialyl.lais~;
see Fig. 2) is recognized
qually
well hy the E
selectin. The result is rationalized
by model building
which indicates
that the two isomers
cJn present
a similar bee to the recqxor.
This
may help to explain some disparate
results concerning
thr recognition
of different
cell [)pes by the E-selectin.
and underscores
the potential
importance
of sialyl Lewis” antigen espression
in malignant
cells. It re
mains to be seen if this ohsenstion
also applies IO the other nvo se
Iectins.
29.
..
POIfiY
MJ. PHILUPS ML, WAYNeIt E. Ntil,l:l,\tAi% E, SINGIIAI AK.
HAKOMOKI S, PAI’ISON JC: CD62 and Endothelial
CelI-Leukocyte Adhesion
Molecule
1 (ELAM-1)
Recognize
the Same
Carbohydrate
Ligand,
Sialyl-Lewis
x. I+-tn‘ ,&ill ,-lc~dri Sii
1: S A 1991, 88:622+622H.
Demonstrdtes
that the cognate
li.gdnds for two of the selectin
have
much in common
and could he identical.
I lo\vc\rr.
the conclusions
are based predominantly
upon inhibition
studies nith multi\alcnt
glycolipids and antixxhohydrate
antihtdies.
30.
.
31.
..
BEHC EL. ROHI~SON MK. WAKNOCI( RA. Bt~Tc~tlitt EC: The Human Peripheral
Lymph
Node Vascular
Addressin
is a Ligand
for LECAM-1,
the Peripheral
Lymph
Node Homing
Receptor. J Cell Biol 1991, 114:3+3+~.
A family
of glvcoproteins
recognized
by the MECA ‘9 antihod!.
molecules
is puhfied. Although
the quantities
obtained
are lo\\.. the m;t
terial allows specific binding of Iymphoc~~es.
and the interaction
i* alx&
ished hy sialidase treatment.
32.
IhW ‘L’. SINGER MS. Feh%w. C. l;tshT IA. Roses SD: Idcntification of a Carbohydrate-based
Endothelial
Ligand for a Lymphocyte
Homing
Receptor.
J Cc/l Hid 1991, 113:1213-1222.
Isolation of sulfated. sialylated glycoproteins
from metabolically
lalwlltul
lymph nodes that fullil all criteria for being the cognate ligands for the
L++ctins.
The challenge
now is to decipher
the slxcilic
sial!l:ttrtl
oligo-saccharide
sequences
on the ma(or 50 kD protein that arc’ rcspon
sible for the spczrilic binding.
..
PICKEK LJ. W’AKNGCK UA. BI’RNS AR. DCXK%:II~~K CM. lWK<; El..
BUTCHER EC: The NeutrophiI
Selectin
LECAM-1
Presents
Carbohydrate
Ligands
to the Vascular
Selectins
ELAM-1
and
GMP-140.
CeN 1991, 66~921-933.
It is suggested
that the L-selectin
on neutrophils
selectiveh.
carries the
primaty oligosaccharide
hgdnds for the I’- and E-sclecrins.
lio\vever.
this
cannot he reconciled
nith the fact that this molecule
ib rApidly lost from
activated
neutrophils.
which continue
to be hound
cluitc well by tht.
E. and P-selectins
33.
.
34.
Pi~orr
R. NEEIIHMI
LA. Emc.wns
RM, W’hi.wi~ C. Pouli~ CStructural
and Functional
Studies
of the Endothelial
Activation Antigen
Endothelial
Leukocyte
Adhesion
Molecule1
Using a Panel of Monoclonal
Antibodies.
J I,,rr,rrrfro/
1991.
147:13&135
lQ\y’~ JR, Kt~iio~~~~-L~‘t’~i.t.~
JF, NAIH KP. IAIL\EN KD. kL\K~is
RM, MACHEK DA. KELLY RJ. ERNST LK: Molecular
Cloning
of
a Human
Fucosyltransferase
Gene that Determines
Expression of the Lewis x and VIM-2 Epitopes
but not Em-l-dependent
Cell Adhesion.
J Hid U~etn 199 I, 266: 1’467- I 7-t7’.
Underscores
the importance
of different
fucosyltransfer‘ties
with differ
ing substrate
specificities
in determining
specific
recognition
hy the se
&tins.
Shows that the fucosyyltransferase
expressed
by the ELFI’ gene
(see 1231) could not have generated
high.afftnity
recognition
by the
35.
..
E-selectin.
ligand.
and
that
the \‘lbl-2
structure
(see
121 1 I is not ;I ye?
good
36.
%tlOl, Q, hltx,Ke KL. SWlW DF. \‘AKKI A, hlcE\eK W. CtlhlhllNG5
RI): The Selectin
CMP-140
Binds to SiaIylated.
Fucosylated
Lactosaminoglycans
on Both Myeloid
and Nonmyeloid
Cells.
J Cdl Hiol 1991, 115:55’-5G-I.
Further
e\iclence
that the non-sialylatecl
Lenis” determinant
cannot be
the sprcilic
ligand for I’ srlectin
(GMP-110).
Esprcssion
of sialylated.
fucos~latt~l
I;tctos:tminclgl!rans
is sulficient
to induce
binding
of the
1’ se&tin.
I lowe\rr.
high-;finit),
binding is only seen \\ith my&id
cells.
This indicates
that such sugar squcnces
are nccessa~.
hut not sufi
cient to medixe
hiologicall!~
rclc\‘ant
binding
by the P+&ctin
..
lIi’:\x(;
K. GI:OFI%O\’
JS. SINGI:H hlS. Rosier SD: A Lymphocyte
Homing
Receptor
(L-Selectin)
Mediates
the IN Vifro
Attachment
of Lymphocytes
to Myelinated
Tracts
of the
Central
Nenvus
System.
./ C‘litr /?IIVSI 1991. BB~l”%l’X3.
An intriguing
obsen’ation
that cognate @rids
for the 1. s&ctin
are not
continecl
to the cnclothclium.
3’.
.
3x.
.
SK;.\CI:I. PO. EIWMUK
AJ. I I.\HHI~OS CT. \\‘~\‘~‘tds~ Whl: Enzymic
Control
of the Expression
of the x Determinant
(CDIS)
in lluman
Myeloid
Cells During
Maturation:
the Regulatory
Role of 6’.Sialyltransferase.
Hltxxl
199 I, 78: 1-til- I-160.
C’nderscorcs
the imlxmancc
of Ixtnch
points in the hio~~~xhcsis
of
oligoxiccharidcs
m determining
the tinal prchluct
~~nthesiztul
by :I given
cell.
39.
T\~G\I>;\ A. O~~~IORI K. T.\K:\II,\\~II
N. ‘l’~t~~t~o&\
K, 1’hG0 A.
ZesrrA
K. I I,lstx;,\a’.\
A. KASSAGI H: Adhesion
of Human
Cancer Cells to Vascular
Endothclium
Mediated
by a Carbohydrate Antigen,
Sialyl Lewis A. /jit&c~r?r
Hio~p/?t:\‘ h’c:x Ci~>~?mr~~r
1991. 179:-1.3%‘19.
40.
\Y:v~\os
SR. I\I,\I 1’. FKSSII: C. GI:oI+‘KI~Y J. SISGI’K M. ROWS
SD. I;\wY IA: The Complement
Binding-like
Domains
of the
Murine
Homing
Receptor
Facilitate
Lectin
Activity.
./ Cc811
Hid 1991. 115:‘.+5-2-l3.
K..\ss:~\ GS. Si’I;R’rtsi 0. Yr( X%\IA\
I-\I. Tiii)ix~
TF: Molecular
Mapping
of Functional
Domains
of the Leukoq-te
Receptor
for Endothelium.
LAM-l.
./ G// /Go/ 1991. 11~:351~35X.
Studies using truncated
constn~cts
and monocIon;~I
anrib{ tclics suggest
that other domains
of the I.-ztflectin
may be important
in rlctcrmining
binding.
In some‘ c:thes. it is dificult
to distinguish
non-specltic
eH&cts
on confomxttion
()I the pnxcm
caused hy the tmncati( )ns from speiilic
changes
in region
cnticaI for the‘ interactions
(sc’c’ :llso I-(O) ).
il.
.
-11.
.
.\1or-rc;o,\t~tcy
Kl:. 051~0KS I.. t1lissrc 1s C. ‘flYv.\KI) K. Got+
I).
\‘A\~AIJ.O C. TAI~K PI. BO\I\%‘IYK K. Loiri, R. I IAKWS J.\l: Acti\ation of EndotheliaI-Leukocyte
Adhesion
Molecule
I (ELAM1) Gene
Transcription.
/‘rtkrVrcl/ :lctrd
.Sci /’ 5 11 1991,
Btk6523452’.
.4 Iirst attempt to esplorc
the cxitical is.4ues rqarcling
the rcgul;ition
of
sclec‘tin esprcssion.
-1.5.
..
KI’VAH K. I’O’I\ Is 1~. Xll’I.I.l;K WA. Sr:\Y.ll:r
I’ Cloning
of
a Human
1 (1.3).Fucosyltransferase
Gene
that
Encodes
ELFI’ but does
not Confer
ELAM-I
Recognition
on Chinese Hamster
Ovary
Cell Trdnsfectants.
./ Hhd Clwt~ I99 I,
266:217’-~71Yi5.
-1-1.
..
~KKIU
D. J.\W~
I’. K;\o N. F0Shl.l. c. AliH;~\ 5. D;\\G1’l’Ih
I’.
N:\\lllil)
hl. KAWC;,\W,\ A. KIM) XI. A\:\ I). KIIX) J. BIG\SI)I.I~
BK: Structural
Requirements
for the Carhohydratc
Ligand
of E-Selectin.
/+oL’ ,&r/l ,+lcoc/ Ssi 1 ’ 5 .I 1991, R8~10.372~~ 103-h.
Careful studies aimed at clclincating
the minimal structural
requirements
ti,r recognition
by the E sclcctin.
including
spccitic gnqx
on individual
moncx~ccharide
components
45.
LI.~~IX’I:SHI:KG JFM. TAN A, J~i~:slto&t~tli
TMAA.
I’~.olic;t~ 1II..
IU’l’KhLo
WA: The Ligand
Recognized
by ELAM-1 on HL60
Cells is not Carried
by N-linked
Oligosaccharides.
/:‘!I). ,I
/,flmrr,ro/
1991, 2 1:3115’-3059.
-16.
.
&Kc; EL, YOV~INO T, Ho-i-r IS. KOI~INWN
MK. W’hKxoc~
Kisitiht0’ro
TK. PICKI% I-J. Bti.ciit%
EC: The Cutaneous
RAW.
Lym-
Selectins
phocyte
Antigen
is a Skin Lymphocyte
Homing
Receptor
for the Vascular
Lectin EndotheIiaI
Cell-leukocyte
Adhesion
Molecule
I. ./ filp hfed 1991. 174:1461-1466.
E-selectin-mcrliatt
recognition
of a specific
suhset
of IymphoqTes.
which do not appt-x
to carry the sialyl-l&s”
determinant
(as determined hy a mon(K‘lonal
antiho+).
I Iowcver,
silid:Lse
treatment
grner
ates the core Lenis” determinant.
47.
SKINNIiR MI’, I.tK:As CM, BI’RNS GF, CIiESTF:KhlAN CN.
MC, GMP-140
Binding
to NeutrophUs
is Inhibited
fated Glycans.
,/ Hid cI.wtt~ 1991, 266:53’I-537-1.
58.
Bl~KliSl~l
by Sul-
4x.
.
ARIWO
A, KOIANII~ W. WAU G, Fw)hlkh:
P. Sri~in B: CD62/PSelectin
Recognition
of Myeloid
and Tumor
CeII Sulfatides.
Cdl 1991. 67:35-i+.
Evidence
that the I’ selcrtin
can recogmze
and hind to a small sulfa&
glycolipid
that &K”S not contain sialic acid. The binding
appears
to hc
calciunl-indrpcndcnt.
ho\vevcr.
and may represent
a distinct
rccognilion path\vay.
49
..
FI~KI’I)A M: LcukosiaIin.
a Major
OGlycan-containing
gIycoprotein
Defining
Leukocyte
Differentiation
and
nancy.
~;~~cthiolo~~
1991, 13-1-356.
An up to date re\icw,
including
discussion
of the cspression
lor;u~~inc~~lycans
on myeloicl cells.
50
,k\Al)A
!vl, I;l ‘HI:KAU’,\
K, bh-I-OH
[;.
G,UlhlllliR<;
<:G.
SiaIylMaIigof Iac
&X3A’l-,\
A:
Structural
Study of the Sugar Chains
of Human
Leukocyte
Cell Adhesion
Molecules
CD 1 I /CD 18. /~iohwris/q~
1991.
30.1561-15’1.
The sialyl-lrwns”
motif 1s present on a neutrophil
adhcslon
pnjrcin
01
the inregrin bmmily. The possibiliv
of a tripartite
recognition
bystern in
valving a cross-over
between the seltvtin
and intcgrin
bmilies
must be
cc )nsidered
.
il.
\‘XRKI A. Diversity
2:Li-N.
52.
IA MP. hltx,Kli KL.
GA. %IXIXII:ILII~
Neutrophil
Adhesion
to Activated
by <;MI’- 140. ,Vtr/ror,
1990. 343.-i’-
5.3
G~,wl.li JK. SKISNER hll’. I~I;KSI~I‘ hlC. VUX\ MA: Prevention
of
Activated
Neutrophil
Adhesion
to Endothelium
by Soluble
Adhesion
Protein
GMPI40.
Scicww
1‘990. 249.4 14-i I’.
C;l:NG JC. Hl:\‘ll~CQl
SM. MI JM. 131~
in
the
SiaIyic
Acids.
G’!~*ctbido~~*
and
1992.
Mclv~~rt~i
TM, l’RF~.(:o.I-I.
GA. fvk:E\r~
RI’: Rapid
Endothelium
Mediated
‘60
54.
.
W’:YIX)S SK. I:~‘w~li C. I,\\KY IA: Neutrophil
InUux
into an
Inflammato~
Site Inhibited
by a Soluble Homing
ReceptorIgG Chimera.
rV&rr,~,
1991, 3+9:1(~~- 16’.
Demon~tratlon
in the inl:ict animal of the potential
role of the 1. sclcctin
111determining
early neutrc)phil
csit into intlsmmatc,n
sites. The rchulth
prc*dicr that the 1. selcvtin Ilgand nit151 bc csprcsstil
by acutely intl;lmc~l
cndc )lhelia.
S\lrllI
CW’. Kl>lllst1m~
‘IX. Allll;\\5
0. I ll’t;lw~
13. Hol’lII1;IY
R, hk:lsnKli
I.\‘. BllKtlliH
E. ,ASl)liHlros
IX:
Chemotactic
Factors
Rcgulatc
Lectin
Adhesion
Molecule
1 (LECAMI)dependent
Neutrophil
Adhesion
to Cytokine.stimulated
Endothelial
CcUs 1,~ M&o, .: C’li,r /PI~W/ 1991, 87:hO9<>lX.
One of three rctarecl p:lpc’rs Iq the s;~nic’ gr~~up (KY atso 1691 ) rh;ll
cc)ncluclc
th;t1 [hc 1. .\cIcc.tin (lECA.\l
I ) mll’it IX in\.otvc+I 111the’ Inrcgrin
lnclcp~ndcnt
binding or ncuuophtt~
tr, :lctlKuecl ~ncl~~lh~lium
I’IUXR l,1. IilSl ll\l( )‘II) TK. S&IIIH 0’.
W!\lw )(:K Kr\. I~1’X’III~H
IlC EIAM-I
is an Adhesion
~Moleculc
for Skin-homing
7
ceus.
I\‘rrlrrrl,
1991, 349.-9(,~-99
I)emc~nstmrion
111% rhc I< sclectin
( EL\hl I ) is in\r)Ivtul
in the cstK:l\:l
3tion
nor only of phagoc?%c. cell5 1n :1cutc 1ntlammalic~n.
1~111;IIx) of :I
suhpopulatlon
of I’ cc’ll~ during chronic. i1ltl;Ulln1:1tion.
5’.
.
l.l’\c:ls~~~~~ I.%‘. CYHI’l.\KY MI. Iw1.Y J hl. I’lX’KlS\ CS. I)A\‘I\
\‘hl. Glh!l%Hosli MA JH. Cytokine-activated
Human
EndotheUaI Monolayers
Support
Enhanced
Neutrophil
Transmigrdtion Via a Mechanism
Involving
both Endothelial-leukocyte
Adhesion
MoleculeI and Intercellular
Adhesion
MoleculcI. ,/ /t,r,,rrr,ro/
1991. 116:lhl’-lh.?S.
Careful
dissection
of the role of multiple
adhesion
~~stcms
In
neutrophll~ndorhelium
inter.1ctions.
mammalian
sialic
acid-binding
lectins
Varki
KYAN-ALING Ll, HA~KARD Do. POSTON RN, THORNHILL MH, LEE
TH: EndotheliaI
Leukocyte
Adhesion
Molecule-l
and Intercellular
Adhesion
Molecule-l
Mediate
the Adhesion
of
EosinophUs
to Endothelial
Cells In Vitro and are Expressed
by Endothelium
in AUergic
Cutaneous
Infkunmation
In
Viva. J Inmrr,~ol
1991, 146:521-528.
SHihitztl Y. S&%w S. GKABER N. GOPM TV, HORGAN KJ. VAN
SF\‘IX~:R
GA NtwhIAii
W: Activation-independent
Binding
of Human
Memory
T Cells to Adhesion
Molecule
ELAM-1.
iVrt/urP
1991, W9:79~XO2.
E\iJence
that E-selectin (EL4M 1) is important
in the steady-state
recognition of memo?
T cells by chronicdlty
inflamed endothelium.
59.
..
60.
.
KCXH AE, Btwtows
JC. ~HAINES GK, CARLOS TM, HARLQX JM,
LEII~O\X:II SJ: lmmunolocalization
of EndotheUaI
and Leukocyte Adhesion
Molecules
in Human
Rheumatoid
and Osteoanhritic
Synovial
Tissues.
Lab Imvsf
1991, 64:313-320.
Evidence
that E-selectin
1EL&ICI- I ) is expressed
constitutively
by endothelium in chronic
arthritic
diseases. Raises the hope that interference
wirh the recognition
of leuctx>Tes
could he of therapeutic
value against
these cc,mmc,n
and debiliwting
disr;Lsrs.
61.
.
~RTINI
0. li.wsfi
GS. MUNKO JM. GRIFFIN JD, TEDDER TF:
Regulation
of Leukocyte
Migration
by Activation
of the
Leukocyte
Adhesion
Molecule-l
(LAM- 1) Selectin.
Nurrrre
1991. 349:69149+.
7 his srud! sho\vs that mysterious
‘acti\:uion
events such as pre\iously
dcscrihed
for rhe intcgrins
aIso occur with the L-selectln
(LAM.1 ). This
manifests
irself ;L< an improvtul
afinin
of pre-existing
receptors
on the
cell surface.
The rapidiv
of the effect is remarkable
and suppoffi
the
notion th:1t it is biologically
relwant.
However,
because PPME (a phosphovlated
yeast mannan)
~~3s used instead of a sialylated
ligand. the
possihiliv
that m3nnose-6-pht,sphate
receptors
were also being detected cannot
be ruled out.
62.
.
I’A’wI. KD. %I~~IEIL\IAV GA, P~!zsco’rt’
SM. ~MCEV!ZR RP, Mc1vn-R~
TM: Oxygen
Radicals
Induce
Human
EndotheUal
Cells to
Express
GMP-140
and Bind NeutrophiIs.
J Cdl Rio1 1991,
I I 2:7.+9-759.
Ikpending
uIx)n the t)pr of stimulus,
rhr kinetics of rxpresr;,)n
of the
P wlectln
on the cell surfnce can he vex different.
63.
.
WON;
\‘~Ix\
Anion
I. .s :I
Evidence
that
clgnizecl.
CS. GAXIILE JR, SKlSSl!R MP. L1iC.ti CIM. BERNIII MC,
MA: Adhesion
Protein
GMPl40
Inhibits
Superoxide
Release
by Human
NeutrophiIs.
Proc N&l Acnd Sci
1991. 88:2397-2401.
binding of a selrctin
may &liver
a signal to the cells rec-
6-l.
Kl’iyww
TW. I Lww~
BC. HOOC.ERWTKF iM, UwrW’ENHERG JFM.
Koos D: Role of EndotheUal
Leukocyte
Adhesion
Molecule1 and Platelet-activating
Factor
in Neutrophil
Adherence
to
IL- 1-prcstimulated
Endothelial
Cells: EndotheliaI
Leukocyte
Adhesion
,Molecule-I
-mediated
CD18 Activation.
.I fr?r?nrr?lo/
1991, 147:1369-13-‘-f.
55.
.
%
..
other
hi.
..
~AW’HIX:F MB. SI+~INGI’R TA: Leukocytes
RoU on a Selectin
at
Physiologic
Flow Rates: Distinction
from
and Prerequisite
for Adhesion
Through
Integrins.
011 1991. 65:H5~+873.
An elegant i,r r*i/n,study
shoning
the rote of shear force in determining
rhc r&rive
importance
of the selectins
and intvgrins
on model memI~T;IIWS. The results tit well nith srudlrs
can-&l
out in intact ystems.
IJ3 K. G;\Ftrr(;I’ss
I’. FESNII: C. SIStilCR MS, L\shT w. KObEN
SD: Lectin-like
Cell Adhesion
Molecule
1 Mediates
Leukocyte
RoUing
in Mesenteric
Venules
In Vim
~J((KM/ 1991,
77:255j-2555.
l)lrect denions~rzit1on
of ;t role for rhc L-se&in
in the ‘rolling‘ of new
rrophils
prior to their arrest and estrL\z:ition
from the bl1xd stream.
This implies that the Lselectin
ligand is expressed
rapiJIy on recently
a~mxtcul
cnclolhelial
SUtidCCS.
66
.
6’
..
\‘ON A>,‘ttl~S
[‘Il. CI~UIREK~ JD. MCEYOY LM. BARRCATX RF.
ARI;OR~ K;-E. IWTCIIEH
EC: Two-step
Model
of LeukocyteEndothelial
CeU Interaction
in Intlammation:
Distinct
Roles
for LECAM-1
and the Leukocyte
bz lntegrins
In \‘iz~o. f%oc
Null Acud Sci 1’ S A 1991, 88:7538-7542.
265
266
Cell regulation
.
A refinement
of a model proposed
earlier by this group
selectins and integrins
act sequentially
and cooperatively.
well supported
by most other recent studies.
68.
in which the
The model is
DC,
ABBAW
0.
KISIiIMOTo
TK,
KOENIG; JM.
MCIN~KE
LV, Swrm
CW:
Diminished
Lectin-.
Epidermal
Growth
Factor-.
Complement
Binding
Domain-cell
Adhesion Molecule-l
on Neonatal
Neutrophils
Underlies
Their
Impaired
CDIS-independent
Adhesion
to Endothelial
Cells
ANDERSON
In
Vitro.
J Inltnrrnol
1991,
lial CeU Ligand to Support
Leukocyte
Adhesion.
J In??vf~??ol
1991. 147:256i-2573.
Further
r\idence
that an Lselectin
ligand is detectable
on acti\:rted
endothelium.
Ass~!; conditions
were critical in dilferentiating
srltu-tin.
mediliattd binding
trom integrin-mtrliated
binding.
‘8.
TK. WAKNOCK
RA. JII’IIA
MA, BI’TCIII% EC, I.%~F C.
IX, SMITH CW: Antibodies
Against
Human
Neutrophil
LECAhl-1
(LAM-I/Leu-8/DREG-56
Antigen)
and Endothelial
Cell ELAM-1
Inhibit
a Common
CD18-indepen.
dent Adhesion
Pathway
In Vitro. Blood 1991, 78:805-X11.
70.
Lo SK. Ltz S, Ri,,\tos RA. L~HH R. Ros,\ M. CIII-R~SX>
G.
WR~CHT SD: Endothelial-leukocyte
Adhesion
Molecule
1
Stimulates
the Adhesive
Activity
of Leukocyte
Integrin
CR3
(CD1 lb/CDlS,
Mac-l,
a,,,bz) on Human
Neutrophils.
./ E.q
Med 1991. 173:1493-1500.
KISHIMOTO
ANDEMON
71.
B~CHNEH
BS. IIXCINSIX
FW. GlhlllHOSI:
MA JH. Newhb!s
W, STTXIIINSKY SA, DI~RSMNTHONY
CP, KI.I~I(
D. Scm%wiH
RF’: Adhesion
of Human
Basophils.
EosinophUs.
and Neutrophils
to Interleukin
l-activated
Human
Vascular
Endothelial
Cells: Contributions
of Endothelial
Cell Adhesion
Molecules.
j E.q ,\lrd 1991. 17331553-1556.
72.
C,utt.os T, KO\W.ZH
N. Szttv.‘ti-ri!
B. ROY% XI. Nli\\‘\t,\\r
1%
WAYNER E. B~tq\l\t~h‘
C. Oseottti
L, Lotsls R. I&RL~% J: Human Monocytes
Bind to Two
Cytokinc-induced
Adhesive
Ligands
on Cultured
Human
Endothelial
Cells: EndothelialLeukocyte
Adhesion
Molecule-l
and Vascular
CeU Adhesion
Molecule-l.
H/t&
1991. 77:226&22-l.
0.
IANI; Cl.. Kwm
S, Kiwivoro
TK. ANIXKSON DC.
I.\‘. Sxtn.tt CW: Canine
Neutrophil
Margination
Mcby Lectin
Adhesion
Molecule1 In Vitro. J Infmrod
147:210--2115.
,\l~l~-r’~~li
diated
1991.
146:3372-3379.
69.
Ani%tisI
I~WAS’T DE. I’;\nil. KD, hlClh’lYHE TM. McE\‘I:K RP. Pfwscol-r
SM, %ih!hiiiKhbw GA: Coexpression
of GMP-140
and PAF by
Endothelium
Stimulated
by Histamine
or Thrombin:
a Juxtacrine
System
for Adhesion
and Activation
of Neutrophils.
J Cd 13iol 1991. 115:223-234.
A \vc’II documented
Jemonstr.ttion
of juxtncrine
‘cross-talk
between ac
ti\Xed endothelium
and atlhrrrnt
ncutrophils,
invohing
pkttclrt
:icti\:lt
mg factor.
‘9.
..
hl~‘U.lG:\N
MS. \‘,\lt\Sl
J, DAME MK. I:\Xli Cl.. Shll’lI I CW.
~L~IxK\oI\:
DC. W~KI) PA: Role of Endothelial-leukocyte
Adhesion
Molecule
1 (ELAM-1)
in Neutrophil-mediated
Lung
Injury
in Rats. ./ <Ii!1 /fr~wl
1991, 88: 139(~1-106.
A \vcII contn~ll~d
stud!. shoning
the importance
of the I:-selecttn
m
facilitating
neutnq~hil
mediated
lung inju? in an intact :mim;tl system.
This strengthens
the lxlief
that l’h~~rnrn:rc~~ltic;~l interfcrcnce
lvith the
selectin hystem could have signilicanr
therapeutic
Xtluc qqinst
naturalI!
occurring
clisc:lses.
X0.
..
Gt’v)lil.
1~11. U;‘li(;\jli~ CD, ToHcEI.uNI
CA. CId\Klili CC. Il;\YNli>
N. Kcvl II1;Is R. Shtrrlt CW’. L.ITI~ LG. Endothelial
Leukoqte
Adhesion
Molecule-l
Mediates
Antigen-induced
Acute
Airway
Inflammation
and Late-phase
Aimay
Obstruction
in
Monkeys.
./ Cli,r /,rc~js/ 1091, 88.l-10’-I-I
11
73.
I IAKW.IW
.
K<x>\ I>. Neutrophil
and
gration
Across
Monolayers
lial Cells: the Contribution
HhKKi 1991, 78:2-z I -LXX
SHlhlIZI’ Y, NEWIAN LX’. &WAI. TV. HOHL~Y KJ. GIWEK N. 13EAIl
LD. VAN SE\FKTEW GA, Slc\w’ S: Four Molecular
Pathways
of T
Cell Adhesion
to Endothelial
Cells: Roles of LFA- 1. VCAM- 1.
and ELAM-1
and Changes
in Pathway
Hierarchy
Under
Different Activation
Conditions.
J Cd Hid 1991. 1 13: I X3- I2 12
Dissection
of the relative roles of three different .ystcms
in the adhesion
of T-cells to rndothelium.
7-i.
WEIU% PF. R~I,
TII, Golit;r. SE. Cllt Ros\o
G. Ir,lrl$ RR: Human EosinophU
Adherence
to Vascular
Endothelium
Mediated
by Binding
to Vascular
CeU Adhesion
‘Molecule
1
and Endothelial
Leukocyte
Adhesion
Molecule
1. I+tr
,Vlr//
Acad .Ei 1: S A 1991. 88:7~3&7~33.
H~WR
AR. KL:NI(FI. SI, ~form
RF III. \Ylilz\
SJ. Regulation
of Transendothelial
Neutrophil
Migration
by Endogenous
Interleukin-8.
.S&nce
1991, 254:9%102.
Demonstration
of a key role for this c)lokinr
in the ‘cross-talk’
bcnvcen
the endothelium
and the neutrophil
following
the Initial recognition
events.
1 (LAM-l,
L-Selectin)
Interacts
with
an Inducible
LIZI ?!‘liwliRc;
JFhl. \‘AS ~IOI’RIK Jr\.
MonoqTe
Adherence
to and Miof ClTokine-activated
Endotbeof CDIH.
ELAM-I.
and VLA--i.
I l.\v).\
K, I(;.~\l<;\vtl \I’. NIvH Al. I lAliovo1<1 5: Downregulation
of GMP-I40
(CD62
or PADGEM)
Expression
on Platelets
b!
&V-dimethyl
and lV,&V-trimethyl
Derivatives
of Spingosine.
/hdJc’ttti.s/t~’
199 I 30: I I &2- I 1686.
76.
..
GHII:I:IS JI).
MoleculeEndothe-
‘I-W.
I kaurs
:\. J:\l11.( )YSl V’lisl’KIcl~
I). JOS!\\ I ‘, Tl Incw I I-G. Homing Receptors
Reexamined:
Mouse
LECAMI
(MEL-I-i
Antigen) is Involved
in Lymphocyte
Migration
into Gut-associated Lymphoid
Tissue.
/:‘rfr ,/ /!,r,?rrr,ro/
I99 I, 2 1:.!925-1929
iLl’NG DYM. PoRI!H JS. C~‘I~L\X RS: Expression
of Endothelial.
Leukocyte
Adhesion
Molecule-l
in Elicited
Late Phase Allergic
Reactions.
J Cli,? Irrl~rsl 1991, 87: 18Oi- 1x09.
Demonstmtion
in human subjects
that the local migration
of inllam
matory cells into allergic lesions may be mt&ttrd
by c)~okinc-inciuc~~l
expression
of E-selectin
1 EL&Ml ).
SPEtlTlNl 0. LlKINSK.45
I%‘. K.4N5As GS, Mt:SHO JM.
GIMBRONE MA JR. TEDIXH 17:: Leukocyte
Adhesion
Ki’l(wtcs
l)!\vt.t:
Sti. FI%I;KIt:\Kt).r C. \‘:\s IXiH VtliKti\ >I: Direct
Intcraction
with
Primed
CD++
CMSRO+
Memory
T Lymphoc!Tes
Induces
Expression
of Endothelial
Leukocyte
Adhesion Molecule-l
and Vmcular
Cell Adhesion
Molecule-I
on
the Surbce
of Vascular
Endotbelial
Cells. /:‘r/r ,/ /murr,,/o/
IWI.
21:2915~2923.
75.
77.
.
HC.
S\\‘llilmx
Carbohydrate
A \‘arkl.
Gilm:m
Cancer
Drive.
SJ: Reverse
Glycobiology:
the LEC-CAMS
Ligdnds.
G!~~cthio/c~~q~~ 1991. 1,71--L-1
Center 0063. I ‘nivrrsiy
of C:tliforni;i.
1~1 lolla. C;llifornia
92093-0063.
I ‘SA.
and
I
San Ikgo.
their
0500