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Adenosine Triphosphate–Induced Shedding of CD23 and L-Selectin (CD62L)
From Lymphocytes Is Mediated by the Same Receptor
but Different Metalloproteases
By B. Gu, L.J. Bendall, and J.S. Wiley
CD23 is a transmembrane protein expressed on the surface
of B-lymphocytes that binds IgE, CD21, CD11b, and CD11c.
High concentrations of soluble CD23 and L-selectin are found
in the serum of patients with B-chronic lymphocytic leukemia (B-CLL). Because extracellular adenosine triphosphate
(ATP) causes shedding of L-selectin via activation of P2Z/
P2X7 receptors expressed on B-CLL lymphocytes, we studied
the effect of ATP on shedding of CD23. ATP-induced shedding of CD23 at an initial rate of 12% of that for L-selectin,
whereas the EC50 for ATP was identical (35 mmol/L) for
shedding of both molecules. Furthermore, benzoylbenzoyl
ATP also produced shedding of CD23 and L-selectin with the
same agonist EC50 values for both (10 mmol/L). Inactivation
of the P2Z/P2X7 receptor by preincubation with oxidized ATP
abolished ATP-induced shedding of both molecules. More-
over, KN-62, the most potent inhibitor for the P2Z/P2X7
receptor, inhibited ATP-induced shedding of both CD23 and
L-selectin with the same IC50 (12 nmol/L). Ro 31-9790, a
membrane permeant zinc chelator that inhibits the phorbolester-stimulated shedding of L-selectin, also inhibited shedding of CD23 from B-CLL lymphocytes. However, the IC50 for
this inhibition by Ro31-9790 was different for L-selectin and
CD23 (83 v 6 mmol/L, respectively). Although L-selectin was
completely shed by incubation of cells with phorbol-ester,
CD23 was not lost under these conditions. The data show
that extracellular ATP induces shedding of L-selectin and
CD23 from B-CLL lymphocytes by an action mediated by the
P2Z/P2X7 receptor. However, different membrane metalloproteases seem to mediate the shedding of L-selectin and CD23.
r 1998 by The American Society of Hematology.
T
Soluble forms of many membrane molecules have been
described, although the mechanisms involved in their production are poorly characterized. Nonphysiological mediators such
as phorbol esters are known to cause shedding of L-selectin by
activating a zinc-containing membrane metalloprotease termed
L-selectin sheddase.11 Recently, extracellular adenosine triphosphate (ATP) has been shown to mediate shedding of L-selectin
from the surface of both normal and leukemic lymphocytes via
activation of the P2Z purinoceptor of these cells.12 The gene for
the human macrophage P2Z receptor has been cloned, and on
the basis of extensive homology with the six described members of the P2X family of receptors, it is proposed that P2Z be
termed P2X7.13,14 The P2Z receptor of lymphocytes shares
many features with this cloned P2X7 receptor, and it is likely
that the two receptors are identical. First, the receptors are
specific for the fully ionized ATP42 species and show a rank
order of agonist potency of 28- & 38-0(4-benzoylbenzoyl) ATP
(BzATP) : ATP . 2-methylthio ATP . ATP-g-S.15 Second,
the receptor-operated channels are highly Ca21 selective, although Ba21 as well as fluorescent dyes such as ethidium1 or
YoPro are also permeants.13,16 Finally, the receptors are inhibited partially by extracellular Na1 and totally by the isoquinoline sulphonamide derivative, KN-62, as well as by the irreversible inhibitor 28, 38 dialdehyde ATP (OxATP).15,17 In this study
we report that extracellular ATP induces shedding of CD23
from B-CLL lymphocytes. The characteristics of CD23 shedding have been compared with L-selectin shedding and the data
suggest that both processes are mediated via the same P2Z/
P2X7 receptor, although the receptor seems to activate different
proteases.
HE CD23 ANTIGEN is a type II transmembrane protein of
45 kD that acts as a low-affinity receptor for IgE (FceRII).
This molecule is expressed on the surface of normal and
malignant B cells, on monocytes, and to a lower extent on T
cells, eosinophils, platelets, and a subset of dendritic cells.1
CD23 is considered a B-cell activation marker because it is
upregulated during B-cell stimulation by interleukin-4 (IL-4),
IL-13, interaction with T cells, or contact with CD40 ligands.2
CD23 contains a C-type lectin domain which acts as the binding
site for IgE, CD21, CD11b, and CD11c and is separated from
the transmembrane domain by a coiled-coil stalk that facilitates
dimer or trimerization.3 Proteolytic cleavage of membranebound CD23 generates a soluble product of 37 kD that can be
further degraded to 33, 25, and 12 kD.4
High levels of soluble CD23 and L-selectin are found in the
serum of patients with B-chronic lymphocytic leukemia (BCLL), suggesting that shedding of these molecules from
malignant lymphocytes is a continuous process. Lower levels of
soluble CD23 and L-selectin are also found in B-cell immunocytomas and low grade non-Hodgkin’s lymphomas, whereas
only tiny amounts of these soluble molecules can be detected in
the sera of normal subjects. These factors suggest that soluble
CD23 and L-selectin in B-CLL are derived from the circulating
pool of lymphocytes and there is some evidence that soluble
CD23 levels may reflect disease activity and be a prognostic
indicator in B-CLL.5-10
From Sydney University Department of Medicine, Nepean Hospital,
Penrith, Australia.
Submitted December 15, 1997; accepted April 2, 1998.
Supported by grants from the National Health & Medical Research
Council of Australia and the New South Wales Cancer Council,
Australia.
Address reprint requests to J.S. Wiley, MD, Sydney University Department of Medicine, Nepean Hospital, Penrith NSW 2750, Australia.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked ‘‘advertisement’’ in accordance with 18 U.S.C. section 1734 solely to indicate
this fact.
r 1998 by The American Society of Hematology.
0006-4971/98/9203-0024$3.00/0
946
MATERIALS AND METHODS
Materials. ATP, BzATP, OxATP, and phorbol 12-myristate 13acetate (PMA) were from Sigma Chemical Co (St Louis, MO). Ro
31-9790 (N-2-((2S)-[(hydroxycarbamoyl)methyl)-4-methylvaleryl]-N1,3-dimethyl- L-valinamide) was a gift from Roche Products Ltd
(Welwyn Garden City, UK). KN-62, 1-[N,O-bis(5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine was from Research Biochemicals, Inc (Natick, MA). Ficoll-Hypaque (density 1.077) was
obtained from Pharmacia (Uppsala, Sweden). Fluorescein isothiocyaBlood, Vol 92, No 3 (August 1), 1998: pp 946-951
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ATP-INDUCED SHEDDING OF CD23 AND L-SELECTIN
nate (FITC)-labeled or purified mouse anti-human monoclonal antibodies (MoAbs) to L-selectin (CD62L) were either the DREG.55 clone
(Bender MedSystems, Vienna, Austria) or the FMC46 clone (DAKO,
Carpinteria, CA). FITC-, phycoerythrin (PE)-conjugated, and purified
mouse anti-human MoAbs to CD23 were the Tü-1 clone from Bender
MedSystems, the Leu-20 clone from Becton Dickson Co (San Jose,
CA), and the MHM6 clone from DAKO. Horseradish peroxidase
(HRP)-conjugated goat anti-mouse IgG was obtained from DAKO.
Enhanced chemiluminescence (ECL) kit was a product of Amersham
(Buckinghamshire, UK). Flow Cytometry standard beads (Quantum 26)
were from Flow Cytometry Standards Co (San Juan, CA).
Source of lymphocytes. Peripheral blood lymphocytes with known
P2Z/P2X7 responses were obtained from six patients with B-CLL and
separated on Ficoll-Hypaque. Monocytes were depleted by plastic
adherence for 1 hour. Cells were then washed once and resuspended in
either Hepes-buffered NaCl medium (145 mmol/L NaCl; 5 mmol/L
KCl; 10 mmol/L Hepes, pH 7.5; 5 mmol/L D-glucose; 0.1% bovine
serum albumin [BSA]) or KCl medium (150 mmol/L KCl; 10 mmol/L
Hepes, pH 7.5; 5 mmol/L D-glucose; 0.1% BSA). Cell morphology
showed that greater than 99% of the mononuclear cells from B-CLL
patients were small mature lymphocytes and immunophenotype showed
93.3 6 8.8% of these lymphocytes typed as CD51, CD191, whereas
5.7 6 2.5% typed as CD31.
Immunofluorescence staining for L-selectin and CD23. Aliquots of
lymphocytes (1.0 3 106/mL) were incubated for up to 30 minutes in
NaCl or KCl medium at 37°C with either ATP, BzATP, or PMA. In some
experiments, lymphocytes were pretreated with 300 µmol/L OxATP for
1 hour. The inhibitors Ro 31-9790 or KN-62 were added 15 minutes
before the addition of ATP or BzATP. The incubation was stopped by
adding an equal volume of cold isotonic Mg21 buffer (20 mmol/L
MgCl; 145 mmol/L NaCl; 5 mmol/L KCl; 10 mmol/L Hepes, pH 7.5).
Cells were washed once and stained with FITC- or PE-conjugated
anti–L-selectin or CD23 MoAbs. The mean channel fluorescence was
collected on a FACScan flow cytometry (Becton Dickinson) in linear
mode. The binding of Leu-20 MoAb to CD23 was independent of Ca21
concentration in the medium.
Western blot for L-selectin and CD23. Lymphocytes (1.0 3 108/
mL) were treated with either 0.2 mmol/L BzATP or 100 nmol/L PMA at
37°C in NaCl medium without BSA plus proteinase inhibitors (5
mmol/L EDTA, 2 µg/mL aprotinin, 0.5 mmol/L phenylmethylsulfonylfluoride, 0.2 mg/mL leupeptin). After centrifugation and collection of
supernates, the cells were washed once and lysed in 1% Triton X-100
containing 50 mmol/L Hepes, pH 7.0, plus proteinase inhibitors as
above for 10 minutes. Cell lysates were clarified by centrifugation at
4000g for 15 minutes at 4°C. Western blotting was performed as
previously described.18 Briefly, samples were separated on a 5% to 20%
gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel
and transferred onto nitrocellulose membranes. Membranes were
blocked overnight in TTBS (20 mmol/L Tris; 150 mmol/L NaCl; 0.5%
Tween 20, pH 7.5) containing 5% skim milk powder. Membranes were
probed with antibodies as indicated. Bound antibodies were detected by
HRP-conjugated goat anti-mouse IgG and enhanced chemiluminescence using an ECL kit (Amersham) according to manufacturer’s
instructions.
Statistics. Mean values 6 SEM are shown, whereas significance of
differences was calculated using a Student’s t-test.
RESULTS
Extracellular ATP causes loss of CD23. Figure 1A and B
shows that both ATP and BzATP, a more potent agonist for the
P2Z/P2X7 receptor, caused rapid shedding of L-selectin from
the surface of B-CLL lymphocytes, as previously described.12
Both agonists for the P2Z/P2X7 receptor also caused disappearance of CD23 from the lymphocytes’ surface (Fig 1A and B), but
947
Fig 1. Time course of ATP- and BzATP-induced loss of CD23 and
L-selectin. B-CLL lymphocytes were incubated with 500 mmol/L ATP
(A) or 100 mmol/L BzATP (B) for the indicated times before labeling
with anti-CD23 (s) or anti–L-selectin (d). Results are expressed as the
mean percentage of initial expression 6SEM (n 5 5).
at a far slower rate than for L-selectin (7% v 60% per minute,
respectively). Lymphocytes incubated in either isotonic NaCl or
KCl showed a small but significant rate of spontaneous CD23
shedding with values of 1% to 3% over 5 minutes. In contrast to
the above results, extracellular ATP did not alter the expression
of CD44, CD45, CD47, CD49d, and HLA-DR on B-CLL
lymphocytes (data not shown).
ATP releases soluble CD23. Western blotting showed the
presence of soluble CD23 in the supernates of B-CLL cells
treated with BzATP, but soluble CD23 was not detected in the
supernates of cells treated with phorbol ester (Fig 2). The
appearance of soluble CD23 (Fig 2, lane 3) was associated with
a loss of cell-associated CD23 in the Triton X-100 lysates (Fig
2, lane 4). Analysis of soluble CD23 in previous studies has
identified multiple fragments of molecular sizes 37, 33, 25, and
12 kD.4 The principal band identified in Fig 2 was 33 kD with a
lesser bands at 27 kD. The bands at 33 kD and 27 kD appeared
as doublets. The significance of this is uncertain.
Agonist dose-response for CD23 shedding. Our previous
results show that ATP induces shedding of L-selectin by agonist
occupancy of P2Z/P2X7 receptors.12 ATP induced the loss of
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948
GU, BENDALL, AND WILEY
Phorbol esters induce shedding of L-selectin but not CD23.
Phorbol esters such as PMA are known to induce shedding of
L-selectin from B-CLL lymphocytes.20-22 Figure 6 shows that
PMA induced shedding of L-selectin with an EC50 of 2 nmol/L.
However, PMA did not affect the expression of CD23 and even
at doses as high as 100 nmol/L, no significant shedding of CD23
was observed.
The shedding of CD23 and L-selectin is inhibited by Ro
31-9790. The hydroxamic acid derivative Ro 31-9790 is a
lipophilic inhibitor of L-selectin sheddase, effective in the 2 to
10 µmol/L range in blocking phorbol-ester–induced shedding of
L-selectin in human lymphocytes.11,23 Ro 31-9790 inhibited
ATP-induced shedding of L-selectin with an IC50 of 82.5 6 38.0
µmol/L. This inhibitor was even more potent in inhibiting
ATP-induced shedding of CD23 with an IC50 of 5.7 6 4.1
µmol/L (P 5 .013, n 5 4) (Fig 7).
CD23 shedding is inhibited by extracellular Ca21. Extracellular ATP-induced shedding of L-selectin is independent of the
presence or absence of Ca21 in the medium,12 a finding we
confirmed in the present study. However, ATP-induced loss of
Fig 2. Appearance of soluble CD23 in the supernatant after
lymphocyte exposure to BzATP but not PMA. Lymphocytes were
treated with 100 nmol/L PMA (lanes 1 and 2) or 0.2 mmol/L BzATP
(lanes 3 and 4) for 30 minutes. CD23 was detected in supernatants
(lanes 1 and 3) or cell lysates (lanes 2 and 4) by Western blotting. Lane
5 is a cell lysate of untreated lymphocytes. No bands were detected
using an irrelevant control antibody.
CD23 from B-CLL lymphocytes with an EC50 of 29.7 6 0.9
µmol/L, which did not differ significantly from the EC50 of
31.3 6 1.2 µmol/L for ATP-induced loss of L-selectin (Fig 3A).
A similar result was obtained with BzATP which caused loss of
CD23 with an EC50 of 11.3 6 1.0 µmol/L and loss of L-selectin
with an EC50 of 11.7 6 0.5 µmol/L (P . .5, n 5 3) (Fig 3B).
CD23 shedding is mediated via P2Z/P2X7 receptors. The
isoquinolinesulfonamide derivative, KN-62, is the most potent
inhibitor of the P2Z/P2X7 receptor described to date.17 The
ATP-induced shedding of both L-selectin and CD23 were
inhibited by KN-62 with an IC50 of 11.2 6 1.2 and 16.0 6 4.1
nmol/L that do not differ significantly (Fig 4). Similar IC50 for
KN-62 have been described for ATP-induced Ba21 and ethidium1
influxes.17 Preincubation of lymphocytes with OxATP gives
irreversible inhibition of the P2Z/P2X7 receptor of both murine
macrophages and human lymphocytes.15,19 Lymphocytes were
preincubated with or without OxATP (300 µmol/L for 60
minutes at 37°C) before incubation with BzATP (100 µmol/L)
in NaCl-media. Figure 5 shows that the shedding of both CD23
and L-selectin was completely abolished by OxATP preexposure. The downstream effects of ATP on lymphocytes are
attenuated in high NaCl media that slows but does not abolish
the shedding of L-selectin from B-CLL lymphocytes.12 Similarly, ATP-induced shedding of CD23 was slower in NaCl
media than in KCl media (data not shown).
Fig 3. Dose response of ATP- and BzATP-induced shedding of
CD23 and L-selectin. B-CLL lymphocytes were incubated with the
indicated concentration of ATP (A) or BzATP (B) for 7 minutes before
labeling with anti-CD23 (s) or for 1.5 minutes before labeling with
anti–L-selectin (d). Results are expressed as mean percentage of
initial expression 6SEM (n 5 3).
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ATP-INDUCED SHEDDING OF CD23 AND L-SELECTIN
Fig 4. KN-62 inhibits ATP-induced shedding of CD23 and L-selectin.
B-CLL lymphocytes were treated with the indicated concentrations of
KN-62 before exposure to 500 mmol/L ATP (7 minutes for CD23 and
1.5 minutes for L-selectin measurements). Cells were then labeled
with anti-CD23 (s) or anti–L-selectin (d) and the results expressed as
the mean percentage of inhibition of shedding (difference of means
not significant, n 5 3).
949
blocked the shedding of L-selectin and CD23 with the same
IC50’s (Fig 4), whereas pretreatment of lymphocytes with
OxATP irreversibly inhibited the ability of P2Z/P2X7 agonists
to induce shedding of either surface molecule.
There has been much recent interest in the nature of the
protease responsible for the shedding of L-selectin. This
enzyme does not cleave soluble substrates and is insensitive to a
wide range of commonly used protease inhibitors, including
diisopropylfluorophosphate, TIMP-1 (tissue inhibitor of metalloproteinase-1), and phosphoramidon.11,23 The only known inhibitors are the hydrophobic hydroxamic acid derivatives such as
Ro 31-9790 or KD-IX-73-4 which chelate zinc, whereas the
water-soluble zinc-chelator o-phenanthroline is ineffective (unpublished observation). This requirement for lipid solubility of
the inhibitor suggests that the enzyme that sheds CD23 contains
zinc in a hydrophobic location, probably within the plasma
membrane. How this enzyme is activated when agonist occupies the P2Z/P2X7 receptor is unknown. Members of the P2X
receptor family have protein structures with two putative
CD23 measured at 15 minutes was inhibited by 34% to 67%
(n 5 5) in the presence of 1 mmol/L Ca21. The inhibitory effect
of other divalent cations on the shedding of CD23 by ATP was
studied. Mn21 was the most potent inhibitor of CD23 loss and
the order of inhibitory potency (at 1 mmol/L divalent concentration) was Mn21 . Ca21 5 Mg21 . Ba21 (data not shown).
Thus, the presence of Ca21 and especially Mn21 increased the
resistance of CD23 to proteolytic shedding by approximately
twofold.
DISCUSSION
Lymphocytes from patients with CLL express large numbers
of receptors for extracellular ATP (P2Z/P2X7 receptors), and
agonist competitive studies have shown only one class of
purinoceptor, the P2Z/P2X7 receptor, is expressed on the
surface of these cells.24 Activation of P2Z/P2X7 receptors
induces multiple downstream effects, of which the best documented is the opening of an ionic channel that is selective for
divalent cations.25,26 A second effect of ATP is to stimulate a
phospholipase D, which on attachment to the plasma membrane, catalyzes hydrolysis of phosphatidylcholine to phosphatidic acid and choline.27,28 A third effect of ATP is to induce the
shedding of L-selectin (CD62L),12 a C-type lectin that is
involved in the adhesive interactions and rolling behavior of
lymphocytes on endothelial cells.29 This study has identified
another effect of ATP on B-CLL lymphocytes: the shedding of
CD23 and appearance of soluble CD23 in the supernate. In
contrast to the rapid shedding of L-selectin, the loss of CD23
induced by ATP was about one order of magnitude slower.
Despite this difference in kinetics, several lines of evidence
show that the ATP-induced loss of CD23, like L-selectin, is
mediated by agonist activation of the P2Z/P2X7 receptor. Thus,
CD23 and L-selectin showed identical dose-response curves for
shedding by either ATP or the more potent agonist BzATP (Fig
3). Moreover, the potent P2Z/P2X7 receptor inhibitor, KN62,
Fig 5. Inhibition of CD23 and L-selectin shedding by OxATP. B-CLL
lymphocytes were treated with (s) or without (d) 300 mmol/L OxATP
before exposure to 100 mmol/L BzATP. Expression of CD23 (A) and
L-selectin (B) was measured and results expressed as the mean
percentage of initial expression 6SEM (n 5 3).
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950
Fig 6. PMA induces shedding of L-selectin but not CD23. B-CLL
lymphocytes were exposed to the indicated concentrations of PMA
for 15 minutes before measurement of CD23 (s) or for 1.5 minutes
before measurement of L-selectin (d). Results are expressed as the
mean percentage of initial expression 6SEM (n 5 6).
transmembrane segments linked by a long extracellular loop
and intracellular N- and C-termini. The P2Z/P2X7 receptor is
unusual in having a long C-terminal tail which not only confers
unique permeability properties to large fluorescent cations,13,14
but also has the potential for interactions with other membrane
molecules such as proteases.
The initial rate of decrease of L-selectin immunoreactivity
was 60% per minute but only 7% per minute for CD23 with
either agonist (Fig 1), indicating an 8.5-fold greater rate of
shedding for L-selectin over CD23. It has been shown that
phorbol ester-induced shedding of L-selectin from human
leukocytes by L-selectin sheddase involves proteolytic cleavage
at a K-S peptide bond.11,30 The structure of CD23 also includes
Fig 7. Ro 31-9790 inhibits ATP-induced shedding of CD23 and
L-selectin. B-CLL lymphocytes were treated with the indicated concentrations of Ro 31-9790 before exposure to 500 mmol/L ATP for 7
minutes for CD23 and 1.5 minutes for L-selectin. CD23 (s) and
L-selectin (d) expression was then determined and the results
expressed as the mean percentage of inhibition of shedding 6SEM
(n 5 3). *, P F .05.
GU, BENDALL, AND WILEY
three K-S bonds in its extracellular domain, although the most
proximal cleavage site is 35 residues distal from the transmembrane domain compared with 10 residues for L-selectin. Assuming the catalytic site for proteolysis is membrane associated,11
and L-selectin sheddase cleaves both membrane proteins, then
purely steric factors may account for the slower rate of CD23
shedding compared with L-selectin. However, recent data using
site-directed mutagenesis has cast some doubt about the specificity of L-selectin sheddase for the K-S bond.31 Our data
support a different hypothesis, namely that two different
proteases are involved in the shedding of L-selectin and CD23.
This latter possibility is supported by the failure of phorbol ester
to shed CD23 (Fig 6) and the different sensitivity of shedding of
L-selectin and CD23 to inhibition by Ro 31-9790 (Fig 7).
Considering the wide range of membrane molecules that are
known to be shed from the surface of leukocytes, it is likely that
many different proteases are involved.32
A number of membrane molecules require extracellular Ca21
to maintain their tertiary or quaternary structure.33 Our data
show that extracellular divalent ions inhibit the ATP-induced
shedding of CD23. This result may reflect the stabilization of
CD23 structure by Ca21 such as shown for the resistance of the
plasma cell membrane glycoprotein, PC-1, to proteolysis and
thermal denaturation.33 However, the structure of the stalk
region of CD23 (where enzymatic cleavage occurs) is an
a-helical coiled-coil that does not contain a recognized Ca21binding domain and is unlikely to be stabilized by Ca21 ions.3
Thus, the mechanism by which Ca21 inhibits ATP-induced
CD23 shedding remains uncertain.
ATP-induced loss of CD23 immunoreactivity from the surface of B-CLL lymphocytes is associated with the appearance
of soluble CD23 in the supernatant (Fig 2). Western analysis of
the supernatant revealed two bands of molecular weights 33 and
27 kD, similar to those previously described in human plasma.34
High levels of both soluble CD23 and soluble L-selectin are
found in the sera of patients with B-CLL, whereas levels of
soluble CD23 have been related both to the tumor load and the
clinical stage of this disease.5-10,21,37 Moreover, soluble CD23
has been proposed as a sensitive and specific marker for disease
activity,6-8 whereas in a complementary study high levels of
cellular CD23 have been correlated with a favorable prognosis
in B-CLL.37 Recent evidence suggests that L-selectin is cleaved
from the surface of leukocytes within seconds during the
process of rolling under hydrodynamic flow38 and it has been
shown that hydroxamic acid-based inhibitors of zinc-dependent
metalloproteases not only slow the rate of leukocyte rolling38
but also inhibit ATP-induced shedding of both L-selectin and
CD23 (Fig 7). Because hydrodynamic shear causes release of
ATP from endothelial cells,39 it is possible that the transient
tethering that characterizes the rolling behavior of leukocytes
may also provide the rapid signal for endothelial ATP release.
This in turn could activate the P2Z/P2X7 receptor in the
microenvironment of the tethered lymphocyte, stimulate the
proteases that are coupled to this receptor, and generate both
soluble L-selectin and soluble CD23.
ACKNOWLEDGMENT
We thank Tina Murphy for typing the manuscript and Roche Products
Ltd for supplying Ro31-9790.
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ATP-INDUCED SHEDDING OF CD23 AND L-SELECTIN
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From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1998 92: 946-951
Adenosine Triphosphate−Induced Shedding of CD23 and L-Selectin
(CD62L) From Lymphocytes Is Mediated by the Same Receptor but
Different Metalloproteases
B. Gu, L.J. Bendall and J.S. Wiley
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