FEMS Immunology and Medical Microbiology 26 (1999) 197^202
New insights into the role of serum amyloid P component,
a novel lipopolysaccharide-binding protein
Carla J.C. de Haas
Eijkman-Winkler Institute, Department of In£ammation, G04.614, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
Received 11 March 1999 ; revised 15 July 1999; accepted 21 July 1999
Abstract
Serum amyloid P component (SAP) is a highly preserved plasma protein named for its ubiquitous presence in amyloid
deposits. Although SAP is described to bind many ligands, no clear biological function has been ascribed to it as yet. This
review summarizes the current knowledge about the protein SAP, its ligands and functional properties. Finally, the author
focuses on the recent finding of the binding of SAP to lipopolysaccharide (LPS) and Gram-negative bacteria and the possible
functional consequences of these interactions. ß 1999 Federation of European Microbiological Societies. Published by
Elsevier Science B.V. All rights reserved.
Keywords : Serum amyloid P component ; Pentraxin ; Alzheimer's disease ; Lipopolysaccharide binding; Lipopolysaccharide neutralization ;
Gram-negative bacterium
1. History of serum amyloid P component
Amyloid P component (AP) was ¢rst discovered as
a glycoprotein present in all amyloid deposits in all
types of amyloidosis, and was found to be identical
to the normal circulating plasma glycoprotein, serum
amyloid P component (SAP). The name P component originated from the discovery that this constituent of amyloid deposits was related to a protein
present in the plasma of healthy individuals. Another
name given to SAP was 9.5SK1 glycoprotein [1]. In a
negative staining electron microscopic study of amyloid extracts the characteristic pentagonal structure
of SAP was ¢rst interpreted as the subunit of aggregated SAP rods, which were believed to be the bulk
of amyloid deposits. Later it was shown that amyloid
deposits are composed of amyloid ¢brils derived
from a range of di¡erent precursor proteins in the
di¡erent manifestations of the disease, whilst SAP is
a minor component associated with the ¢brils as a
consequence of its capacity to bind speci¢c determinants shared by all types of amyloid ¢brils [2,3].
For a short time SAP was believed to be the fourth
subcomponent of the C1 component of the complement system and assigned the name C1t. Later,
when SAP was demonstrated to bind agarose in a
calcium-dependent way, it was recognized that SAP
was not C1t, but a contaminating component in the
isolation of the authentic C1 components via agarose
[4].
2. Family of pentraxins
SAP belongs to the family of pentraxins (from the
Greek words for ¢ve (penta) berries (ragos)), a
0928-8244 / 99 / $20.00 ß 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.
PII: S 0 9 2 8 - 8 2 4 4 ( 9 9 ) 0 0 1 4 8 - 0
FEMSIM 1131 17-11-99
198
C.J.C. de Haas / FEMS Immunology and Medical Microbiology 26 (1999) 197^202
superfamily of plasma proteins characterized by their
pentameric assembly and calcium-dependent ligand
binding [5]. Human SAP displays 51% amino acid
homology with C-reactive protein (CRP), the classical acute-phase protein found in humans, another
member of the pentraxin family. In contrast to
CRP, SAP is constitutively present in human serum
at 30^50 Wg ml31 , with a maximum twofold increase
during sepsis, while it is an acute-phase reactant in
mice [6]. Closely related proteins sharing similar sequences, structure and properties are present in all
vertebrates so far investigated, and even in some invertebrates, including the most evolutionarily distant
horseshoe crab (Limulus polyphemus) [7]. The highly
conserved family of pentraxins was thought to consist solely of proteins of about 25 kDa. Recently,
other more distantly related proteins have been identi¢ed in which only the C-terminal halves show characteristic features of the pentraxin family [8]. These
'long' pentraxins with molecular masses around 40^
50 kDa include PTX3 or TSG-14, a cytokine-inducible human protein of endothelial cells, ¢broblast,
hepatocytes and mononuclear phagocytes; neuronal
activity-regulated pentraxin (NARP), a neuronal
pentraxin which is dynamically regulated by neuronal activity promoting neurite outgrowth; apexin, a
sperm acrosomal protein, and XL-PXN1, a protein
in the amphibian Xenopus laevis [9].
3. Structure of SAP
SAP is a decameric serum glycoprotein composed
of identical 25.5-kDa subunits non-covalently associated in two pentameric rings interacting face to face.
In the presence of high concentrations of calcium
SAP rapidly aggregates and precipitates, but in the
absence of calcium or in the presence of EDTA it
forms a very stable decameric structure, although
there is some debate whether native human SAP exists in its decameric or pentameric form. In contrast,
CRP is composed of a single pentameric ring that is
stable in the presence of calcium and does not form
decamers [10]. Recently, the three-dimensional (3D)
structure of human SAP was elucidated at high resolution by X-ray analysis. The SAP pentamer consists of ¢ve subunits of 204 amino acid residues, each
with a closely similar 3D structure constructed from
antiparallel L-strands arranged in two sheets forming
a jelly roll fold. Calcium binding occurs on one site
of the pentamer, on the surface composed of the
more concave L-sheets. On the opposite more planar
face, each subunit has an K-helical segment. The
subunit interactions consist of hydrogen bonds between main-chain peptide groups, three salt bridges
and some hydrophobic contacts. Electron microscopy has shown that the SAP pentamers are packed
face to face. It is believed that the faces in contact
are those carrying the K-helix, as the calciumdependent ligand-binding sites are on the other
face, and because in this arrangement the calciumcontaining L-sheets of each pentamer are accessible
[6].
4. Ligands binding to SAP
After the ¢rst report about calcium-dependent
binding of SAP to agarose, SAP has been reported
to bind to glycosaminoglycans, especially heparin,
heparan sulfate and dermatan sulfate, to mannoseterminated glycans, and to glycans with preterminal
galactose residues [4,6]. However, the best characterized carbohydrate ligand of SAP is the pyruvate
acetal of galactose that occurs in agarose and
which is synthesized in a monosaccharide form as
methyl 4,6-O-(1-carboxyethylidene)-L-D-galactopyranoside (MoLDG) [11]. SAP also interacts speci¢cally
with phosphorylethanolamine (PE), while CRP has
been identi¢ed to bind phosphorylcholine (PC) [12].
Native SAP also binds avidly to DNA and to chromatin, and is the single protein from whole serum
that shows calcium-dependent binding to these ligands at physiological pH and ionic strength. Furthermore SAP binds in vitro to nucleoli in the intact
nuclei of cells permeabilized by ¢xation, but not to
any other nuclear or cytoplasmic structures. The interaction with chromatin completely displaces histone H1 and thereby solubilizes this otherwise highly
insoluble material. SAP also binds to extracellular
chromatin in vivo [6,13]. SAP and also CRP contain
nuclear recognition motifs in their sequences. In the
case of microinjection into living cells in vitro these
pentraxins enter the nucleus and bind to their respective speci¢c ligands [14]. The physiological relevance
of SAP binding to nuclear components has not been
FEMSIM 1131 17-11-99
C.J.C. de Haas / FEMS Immunology and Medical Microbiology 26 (1999) 197^202
clari¢ed yet, but it is believed to play a role in the
binding and clearance of host- or pathogen-derived
cellular debris at sites of in£ammation [5].
5. Functional properties of SAP
The physiological functions of SAP are not
known, although the fact that no SAP de¢ciencies
in man or animals have been reported yet suggests
that they are likely to be important. However,
recently SAP knockout mice were produced that
developed normally and were fertile, which suggests
that despite the evolutionary conservation and
presumably signi¢cant physiological function of
SAP, blocking SAP binding in vivo may not
have major adverse e¡ects [15]. A number of potentially biologically signi¢cant properties of SAP have
been reported, but their relevance in vivo is not
clear.
5.1. SAP binding to complement components
Many reports describe the interaction of SAP with
complement components. In 1975 Assimeh and
Painter even thought SAP to be C1t, the fourth subcomponent of the C1 molecule, because of the persistent calcium-dependent association of the protein
with the other C1 subcomponents [4]. It has been
reported that SAP binds to the collagen-like region
of C1q in the presence of calcium thereby activating
the classical pathway [16]. All SAP in serum is complexed with C4b-binding protein (C4BP), although
some claim that only SAP immobilized on solid
phase can bind C4BP. There is some debate whether
SAP binding to C4BP in£uences the function of
C4BP. Some reports claim that SAP has no e¡ect
on the function of C4BP whereas others say that
SAP does activate the classical pathway by inhibiting
the ability of C4BP to function as a cofactor for
factor I in the degradation of C4b [17,18]. Most
SAP-ligand interactions are calcium-dependent. Barbashov et al., however, found a calcium-independent
binding of SAP to the C5b6 complex [19]. This interaction seems to have no implications for the subsequent formation of the membrane attack complex,
as the SAP-C5b6 complex bound C7 with almost the
same hemolytic activity as C5b6 alone.
199
5.2. SAP binding to cells
There are a few articles demonstrating binding of
SAP to cells. Landsmann et al. show 300 000 lowa¤nity and about 30 000 high-a¤nity binding sites
on normal polymorphonuclear leukocytes (PMN)
[20]. SAP was found to be degraded by enzymes
from PMN to yield a mixture of low-molecularmass peptides, which inhibited the binding of SAP
to PMN. Others also demonstrated binding of SAP
to mouse macrophages [21,22]. The receptor binding
SAP probably is the cation-dependent mannose 6phosphate receptor, as mannose sugars inhibited
the binding. SAP was demonstrated to induce enhancement of the macrophage listericidal activity,
although it did not alter the extent of phagocytosis
by macrophages of opsonized Listeria monocytogenes, nor was SAP opsonic for listeria [22].
5.3. SAP binding to bacteria
Hind et al. found that SAP has a calcium-dependent binding speci¢city for MoLDG. SAP bound to
Klebsiella rhinoscleromatis, the cell wall of which is
known to contain this particular cyclic pyruvate acetal of galactose. SAP also bound to Streptococcus
pyogenes and to a much lesser extent to other bacteria with a similar carbohydrate structure. According to this report SAP did not bind to Escherichia
coli [11].
5.4. SAP and the brown recluse spider
The brown recluse spiders (Loxosceles reclusa), together with widow spiders and tarantulas, belong to
the group of most poisonous spiders. They are found
primarily in the Midwest of the USA. The spider
commonly lives in basements and garages of houses
and often hides behind boards and boxes. The severity of a bite may vary. Often there is a systemic
reaction within 24^36 h characterized by restlessness,
fever, chills, nausea, weakness, and joint pain. Where
the bite occurs there is often tissue death and skin is
sloughed o¡. In some severe cases a wound may
develop that lasts several months. In 1990, Gates
and Rees showed that sphingomyelinase D, puri¢ed
from the venom of the brown recluse spider, induces
platelet aggregation and serotonin secretion. More
FEMSIM 1131 17-11-99
200
C.J.C. de Haas / FEMS Immunology and Medical Microbiology 26 (1999) 197^202
important, however, was that these sphingomyelinase e¡ects only occurred in the presence of SAP [23].
The data reported suggest a function for SAP in a
clinical disorder of the skin which is characterized by
prolonged in£ammation and delayed healing. This
was the ¢rst demonstration of a biological role for
SAP at a site of tissue injury and in£ammation.
6. Role of SAP in Alzheimer's disease
Extracellular deposition of amyloid ¢brils is responsible for the pathology in the systemic amyloidoses, including that of Alzheimer's disease. SAP
binds to all types of amyloid ¢brils and is a universal
constituent of systemic amyloid deposits, and amyloid deposits localized in the brain associated with
Alzheimer's disease and the transmissible spongiform
encephalopathies (prion diseases) [24,25]. Until now
no evidence has been found that SAP mRNA is expressed by brain or any other organ tested except the
liver. These ¢ndings strongly imply that this relatively large protein extravasates from the circulation
possibly via a leaky blood-brain barrier, but some
kind of active transport cannot be ruled out yet.
Alzheimer's L-amyloid peptide (AL) is the principal
component of amyloid deposits in the brain parenchyma and within the cerebromeningeal vasculature
in Alzheimer's disease. The role of SAP in cerebral
amyloidosis as related to Alzheimer's disease is unknown. Neither the mechanism involved in the localization or binding of SAP to cerebral amyloid deposits nor the temporal relationship between SAP
accumulation and amyloid deposition is clear. It
has been shown that SAP can bind to synthetic AL
at physiological calcium concentrations. Since SAP is
resistant to proteases in the presence of calcium, the
binding of SAP to soluble AL and L-amyloid ¢brils
would give pathological e¡ects on ¢bril formation
and persistence of L-amyloid in Alzheimer's disease
[26]. Indeed, SAP binding to the amyloid ¢brils of
Alzheimer's disease was shown to prevent proteolysis
of these amyloid ¢brils [27]. However, the binding of
SAP to AL has also been demonstrated to inhibit the
formation of L-peptide ¢brils. SAP was found to
inhibit ¢bril formation and to increase the solubility
of the peptide in a dose-dependent manner in vitro
[28]. Recently, with the construction of SAP knock-
out mice, two groups demonstrated that SAP signi¢cantly accelerates the deposition of systemic amyloid
A amyloidosis [15,29]. This was the ¢rst demonstration of the participation of SAP in the pathogenesis
of amyloidosis in vivo, suggesting that inhibition of
SAP binding to amyloid ¢brils is an attractive therapeutic target in a range of serious human diseases,
including Alzheimer's disease.
7. SAP binding to lipopolysaccharide
Recently, we demonstrated the binding of SAP to
lipopolysaccharide (LPS) [30]. LPS, or endotoxin, is
the major component of the outer membrane of
Gram-negative bacteria and is a major distinguishing
factor between Gram-negative and Gram-positive
bacteria. LPS consists of three main structural elements: the O-speci¢c polysaccharide chain, the core
region and the lipid A moiety. The O-speci¢c chain is
the most variable part of the LPS molecule and
therefore determines the serological type of LPS
and the Gram-negative bacteria. In contrast, the lipid A moiety is the most conserved part of the LPS
molecule. Based on the presence or absence of the Ospeci¢c chain bacterial LPS is characterized as an S
(smooth) or an R (rough) type, respectively, named
after the appearance of the colonies of these bacteria
formed on agar plates [31]. It was shown that SAP
bound to rough as well as smooth types of LPS, via
its lipid A part, but the highest a¤nity was shown to
rough types of LPS. Using an LPS-coated sensor
chip, we demonstrated that the binding a¤nity of
SAP for LPS from Salmonella minnesota strain
R595 (ReLPS) was 3.9 nM [32]. This value was comparable to published binding a¤nities of other well
described LPS-binding proteins. Using a panel of
overlapping 15-mer synthetic peptides of SAP, three
LPS-binding regions within the SAP molecule were
identi¢ed, comprising amino acids 27^39 [30], 61^75
and 186^200. All three SAP-derived peptides were
able to inhibit the LPS-induced activation of human
phagocytes in the presence of human blood. Moreover, the 15-mer SAP-derived peptide, pep186^200,
showed protection against LPS-induced septic shock
in mice [33], indicating a potential use of this peptide
in the defense against Gram-negative sepsis in humans. Besides binding of SAP to LPS in its isolated
FEMSIM 1131 17-11-99
C.J.C. de Haas / FEMS Immunology and Medical Microbiology 26 (1999) 197^202
201
form, SAP was also demonstrated to bind to Gramnegative bacteria, especially those expressing rough
LPS, like the galactose epimerase-de¢cient mutant of
E. coli O111:B4, E. coli J5. Moreover, SAP also
bound to some Gram-negative bacteria expressing
short LPS or lipo-oligosaccharide (LOS), such as
Haemophilus in£uenzae, Campylobacter jejuni and
Chlamydia pneumoniae (C.J.C. de Haas, manuscript
in preparation). LOS has similar lipid A structures as
LPS, but it contains oligosaccharide structures limited to around 10 non-repeating saccharide units
[34]. These binding data seem in contrast with the
¢ndings of Hind et al., who could not demonstrate
binding of SAP to E. coli, but they probably only
tested E. coli strains expressing smooth types of LPS.
We were also unable to show binding of SAP to, for
example, the smooth strain E. coli O111:B4.
against Gram-negative sepsis. LBP enhances LPS-induced cell activation, but it also augments high-density lipoprotein (HDL)-mediated LPS neutralization
[35]. A same bivalent function is described for
sCD14. sCD14 is required to activate CD14-negative
cells, such as endothelial, epithelial, and smooth
muscle cells. On the other hand, the neutralization
of LPS mediated by LBP and HDL is strongly accelerated in the presence of sCD14 [36], suggesting
an important role for sCD14 also in the neutralization of LPS. Although more research is needed to
draw strong conclusions, SAP could serve as a
downmodulator of bacteria-driven in£ammatory responses while leaving host-driven (antibody-mediated) responses intact, thereby ¢ne-tuning and balancing the in£ammatory response in Gram-negative
infections.
8. Outlook
References
It is di¤cult to speculate on the physiological role
of SAP binding to LPS in vivo. SAP has been described to bind to granulocytes via speci¢c receptors
[20^22]. Whether SAP binding to phagocytes plays a
role in vivo is questionable. Firstly, in our hands
phagocytes bound hardly any SAP, certainly when
compared to Gram-negative bacteria, which demonstrated a much higher binding of SAP. Secondly,
others could not show any opsonic or other function
for SAP with respect to its binding to phagocytes
[22]. The ¢nding that SAP demonstrates a considerable binding to Gram-negative bacteria expressing
short types of LPS suggests that SAP plays a role
in the pathogenesis of these bacteria, especially as we
recently demonstrated that binding of SAP strongly
inhibited the C3 deposition on these Gram-negative
bacteria, via the classical pathway of the complement
system, in the absence of speci¢c antibodies (C.J.C.
de Haas, manuscript in preparation). As complement
can have both protecting and bene¢cial e¡ects as
well as detrimental devastating e¡ects on the host
defense, these ¢ndings suggest that SAP plays a regulatory role in innate immunity, especially when
Gram-negative bacteria are involved. Besides SAP,
LPS-binding protein (LBP) and soluble CD14
(sCD14), other important LPS-binding proteins in
plasma, seem to play a regulatory role in the defense
[1] Cathcart, E.S., Shirahama, T. and Cohen, A.S. (1967) Isolation and identi¢cation of a plasma component of amyloid.
Biochim. Biophys. Acta 147, 392^393.
[2] Glenner, G.G. (1980) Amyloid deposits and amyloidosis ^ the
L-¢brilloses. I. New Engl. J. Med. 302, 1283^1292.
[3] Tan, S.Y. and Pepys, M.B. (1994) Amyloidosis. Histopathology 25, 403^414.
[4] Pepys, M.B., Baltz, M.L., de Beer, F.C., Dyck, R.F., Holford,
S. and Breathnach, S.M. (1982) Biology of serum amyloid P
component. Ann. NY Acad. Sci. 389, 286^298.
[5] Gewurz, H., Zhang, X.H. and Lint, T.F. (1995) Structure
and function of the pentraxins. Curr. Opin. Immunol. 7, 54^
64.
[6] Emsley, J., White, H.E., O'Hara, B.P., Oliva, G., Srinivasan,
N., Tickle, I.J., Blundell, T.L., Pepys, M.B. and Wood, S.P.
(1994) Structure of pentameric human serum amyloid P component. Nature 367, 338^345.
[7] Pepys, M.B., Dash, A.C., Fletcher, T.C., Richardson, N.,
Munn, E.A. and Feinstein, A. (1978) Analogues in other
mammals and in ¢sh of human plasma proteins C-reactive
protein and amyloid P component. Nature 273, 168^170.
[8] Goodman, A.R., Cardozo, T., Abagyan, R., Altmeyer, A.,
Wisniewski, H.G. and Vilcek, J. (1996) Long pentraxins : an
emerging group of proteins with diverse functions. Cytokine
Growth Factor Rev. 7, 191^202.
[9] Pepys, M.B., Booth, D.R., Hutchinson, W.L., Gallimore,
J.R., Collins, P.M. and Hohenester, E. (1997) Amyloid P
component. A critical review. Amyloid Int. J. Exp. Clin. Invest. 4, 274^295.
[10] Ashton, A.W., Boehm, M.K., Gallimore, J.R., Pepys, M.B.
and Perkins, S.J. (1997) Pentameric and decameric structures
in solution of serum amyloid P component by X-ray and
FEMSIM 1131 17-11-99
202
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
C.J.C. de Haas / FEMS Immunology and Medical Microbiology 26 (1999) 197^202
neutron scattering and molecular modelling analyses. J. Mol.
Biol. 272, 408^422.
Hind, C.R., Collins, P.M., Baltz, M.L. and Pepys, M.B.
(1985) Human serum amyloid P component, a circulating lectin with speci¢city for the cyclic 4,6-pyruvate acetal of galactose. Interactions with various bacteria. Biochem. J. 225, 107^
111.
Schwalbe, R.A., Dahlback, B., Coe, J.E. and Nelsestuen, G.L.
(1992) Pentraxin family of proteins interact speci¢cally with
phosphorylcholine and/or phosphorylethanolamine. Biochemistry 31, 4907^4915.
Pepys, M.B., Booth, S.E., Tennent, G.A., Butler, P.J. and
Williams, D.G. (1994) Binding of pentraxins to di¡erent nuclear structures : C-reactive protein binds to small nuclear ribonucleoprotein particles, serum amyloid P component binds
to chromatin and nucleoli. Clin. Exp. Immunol. 97, 152^157.
Du Clos, T.W., Mold, C. and Stump, R.F. (1990) Identi¢cation of a polypeptide sequence that mediates nuclear localization of the acute phase protein C-reactive protein. J. Immunol. 145, 3869^3875.
Botto, M., Hawkins, P.N., Bickersta¡, M.C.M., Herbert, J.,
Bygrave, A.E., McBride, A., Hutchinson, W.L., Tennent,
G.A., Walport, M.J. and Pepys, M.B. (1997) Amyloid deposition is delayed in mice with targeted deletion of the serum
amyloid P component gene. Nature Med. 3, 855^859.
Bristow, C.L. and Boackle, R.J. (1986) Evidence for the binding of human serum amyloid P component to Clq and Fab.
Mol. Immunol. 23, 1045^1052.
Garcia de Frutos, P., Hardig, Y. and Dahlback, B. (1995)
Serum amyloid P component binding to C4b-binding protein.
J. Biol. Chem. 270, 26950^26955.
Sorensen, I.J., Nielsen, E.H., Andersen, O., Danielsen, B. and
Svehag, S.E. (1996) Binding of complement proteins C1q and
C4bp to serum amyloid P component (SAP) in solid contra
liquid phase. Scand. J. Immunol. 44, 401^407.
Barbashov, S.F., Wang, C. and Nicholson-Weller, A. (1997)
Serum amyloid P component forms a stable complex with
human C5b6. J. Immunol. 158, 3830^3835.
Landsmann, P., Rosen, O., Pontet, M., Pras, M., Levartowsky, D., Shephard, E.G. and Fridkin, M. (1994) Binding of
human serum amyloid P component (hSAP) to human neutrophils. Eur. J. Biochem. 223, 805^811.
Siripont, J., Tebo, J.M. and Mortensen, R.F. (1988) Receptormediated binding of the acute-phase reactant mouse serum
amyloid. Cell. Immunol. 117, 239^252.
Singh, P.P., Gervais, F., Skamene, E. and Mortensen, R.F.
(1986) Serum amyloid P-component-induced enhancement of
macrophage listericidal activity. Infect. Immun. 52, 688^694.
Gates, C.A. and Rees, R.S. (1990) Serum amyloid P component: Its role in platelet activation stimulated by sphingomyelinase D puri¢ed from the venom of the brown recluse spider
(Loxosceles reclusa). Toxicon 11, 1303^1315.
[24] Coria, F., Castano, E., Prelli, F., Larrondo-Lillo, M., van
Duinen, S., Shelanski, M.L. and Frangione, B. (1988) Isolation and characterization of amyloid P component from Alzheimer's disease and other types of cerebral amyloidosis. Lab.
Invest. 58, 454^458.
[25] Duong, T., Pommier, E.C. and Scheibel, A.B. (1989) Immunodetection of the amyloid P component in Alzheimer's disease. Acta Neuropathol. (Berl.) 78, 429^437.
[26] Hamazaki, H. (1995) Ca(2+)-dependent binding of human
serum amyloid P component to Alzheimer's beta-amyloid peptide. J. Biol. Chem. 270, 10392^10394.
[27] Tennent, G.A., Lovat, L.B. and Pepys, M.B. (1995) Serum
amyloid P component prevents proteolysis of the amyloid ¢brils of Alzheimer disease and systemic amyloidosis. Proc.
Natl. Acad. Sci. USA 92, 4299^4303.
[28] Janciauskiene, S., Garcia de Frutos, P., Carlemalm, E., Dahlback, B. and Eriksson, S. (1995) Inhibition of Alzheimer betapeptide ¢bril formation by serum amyloid P component.
J. Biol. Chem. 270, 26041^26044.
[29] Togashi, S., Lim, S.K., Kawano, H., Ito, S., Ishihara, T.,
Okada, Y., Nakano, S., Kinoshita, T., Horie, K., Episkopou,
V., Gottesman, M.E., Costantini, F., Shimada, K. and Maeda, S. (1997) Serum amyloid P component enhances induction
of murine amyloidosis. Lab. Invest. 77, 525^531.
[30] de Haas, C.J.C., Van der Tol, M.E., Van Kessel, K.P.M.,
Verhoef, J. and Van Strijp, J.A.G. (1998) A synthetic lipopolysaccharide (LPS)-binding peptide based on amino acids 27^
39 of serum amyloid P component inhibits LPS-induced responses in human blood. J. Immunol. 161, 3607^3615.
[31] Raetz, C.R.H. (1990) Biochemistry of endotoxins. Annu. Rev.
Biochem. 59, 129^170.
[32] de Haas, C.J.C., Haas, P.-J., Van Kessel, K.P.M. and Van
Strijp, J.A.G. (1998) A¤nities of di¡erent proteins and peptides for lipopolysaccharide (LPS) as determined by biosensor
technology. Biochem. Biophys. Res. Commun. 252, 492^
496.
[33] de Haas, C.J.C., Van der Zee, R., Benaissa-Trouw, B., Van
Kessel, K.P.M., Verhoef, J. and Van Strijp, J.A.G. (1999)
Lipopolysaccharide (LPS)-binding peptides derived from serum amyloid P component neutralize LPS. Infect. Immun.
67, 2790^2796.
[34] Preston, A., Mandrell, R.E., Gibson, B.W. and Apicella,
M.A. (1996) The lipooligosaccharides of pathogenic gramnegative bacteria. Crit. Rev. Microbiol. 22, 139^180.
[35] Wurfel, M.M., Kunitake, S.T., Lichenstein, H., Kane, J.P.
and Wright, S.D. (1994) Lipopolysaccharide (LPS)-binding
protein is carried on lipoproteins and acts as a cofactor in
the neutralization of LPS. J. Exp. Med. 180, 1025^1035.
[36] Wurfel, M.M., Hailman, E. and Wright, S.D. (1995) Soluble
CD14 acts as a shuttle in the neutralization of lipopolysaccharide (LPS) by LPS-binding protein and reconstituted high
density lipoprotein. J. Exp. Med. 181, 1743^1754.
FEMSIM 1131 17-11-99