|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1317-1323
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGYAU#0
From the School of Chemical Engineering and Materials Science,
University of Oklahoma, Norman, Oklahoma; the W. K. Warren Medical
Research Institute, Departments of Medicine and Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center,
Oklahoma City, Oklahoma; and the Cardiovascular Biology Research
Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
Platelet microparticles (PMPs) are released from activated platelets
and express functional adhesion receptors, including P-selectin, on
their surface. PMP concentrations are elevated in many disorders, and
their role in accelerating coagulation has been studied. However, their
role in leukocyte aggregation has not been defined. We hypothesized
that P-selectin-expressing PMPs bridge leukocytes that express
P-selectin glycoprotein ligand-1 (PSGL-1), thereby allowing them to
interact under flow conditions. PMPs were isolated from platelet-rich
plasma or were generated by activating washed platelets with calcium
ionophore. PMPs increased transient adhesion of flowing
HL-60 cells or neutrophils to HL-60 cells or neutrophils
prebound to the surface of a parallel plate flow chamber. Homotypic
neutrophil interactions are initiated by the binding of L-selectin to
PSGL-1. However, even when L-selectin function was blocked, PMPs
allowed flowing neutrophils to aggregate and to interact with
PSGL-1-expressing cells prebound to the surface of the flow chamber.
The microparticle-mediated cell interactions occurred at lower shear
stresses than those mediated by L-selectin. PMPs may enhance
leukocyte aggregation and leukocyte accumulation on selectin-expressing
substrates, especially in diseases where the concentration of the
particles is elevated.
(Blood. 2000;95:1317-1323)
One of the most important functions of the immune
system is the recruitment of leukocytes to areas of infection or tissue damage. Leukocytes first leave the central stream of flowing blood and
roll along activated endothelial cells lining the blood vessel wall.
The selectin family of adhesion molecules largely mediates this initial
rolling interaction,1-3 although some integrins are capable of mediating cell rolling on the
endothelium.4,5 In an integrin-mediated process, the
rolling leukocytes then adhere tightly to the vessel wall, which allows
them to emigrate between endothelial cells into areas of infection or injury.
The selectin family of adhesion molecules consists of 3 structurally
related molecules. E-selectin is expressed on the surface of
cytokine-stimulated endothelial cells. P-selectin is constitutively expressed in platelet and endothelial cell secretory granules from
which it can be rapidly deployed on the surface of these cells in
response to agonists. L-selectin is constitutively expressed on
circulating leukocytes. The leukocyte ligand for P-selectin is
P-selectin glycoprotein ligand-1 (PSGL-1).6
L-selectin binds to multiple ligands including peripheral node
addressin (PNAd) expressed on certain endothelial cells and
to PSGL-1 and other ligands expressed on
leukocytes.7-9 E-selectin binds to multiple carbohydrate
ligands expressed on leukocytes including those on PSGL-1.1,3,6
The adhesion mediated by selectins can be broadly classified into
2 categories: primary adhesion, where a flowing leukocyte attaches
directly to the surface, and secondary adhesion, where a circulating
leukocyte first interacts with an adherent leukocyte before attaching
to the surface. Both mechanisms lead to accumulation of flowing cells
on the surface.8,10,11 Primary adhesions are mediated by
the binding of immobilized P- or E-selectin to ligands displayed on the
surface of flowing leukocytes. Secondary adhesions require L-selectin
binding to PSGL-18 or perhaps to other carbohydrate ligands
displayed on leukocytes.9,11 An important difference
between cell interactions mediated by L-selectin from those mediated by
P- or E-selectin is that L-selectin-ligand bonds dissociate much
faster. L-selectin-mediated rolling is faster than rolling
mediated by P- or E-selectin,12 and L-selectin requires a threshold shear stress to initiate rolling.13
Activated platelets attached to a site of injury on the vessel
wall express P-selectin and support the rolling of leukocytes in
the presence of shear stress.14-18 The ability
of activated platelets to bind to leukocytes might enhance leukocyte
accumulation on the vascular surface, leukocyte aggregation, and
thrombus formation.19-22 From their plasma membrane,
activated platelets also release membrane fragments that express
functional surface receptors including P-selectin.23-26
Platelet microparticles (PMPs) provide a catalytic surface that
accelerates coagulation,27-29 and they can bind to neutrophils.30 The potential role of PMPs in
enhancing leukocyte-leukocyte interactions has not been investigated.
We investigated the possibility that PMPs could use P-selectin to
bridge leukocytes, thereby enhancing leukocyte aggregation and
accumulation of flowing leukocytes on a selectin substrate.
Materials
Proteins
Antibodies We purchased antihuman CD43 monoclonal antibodies (mAbs) (clone DF-T1; Sigma Chemical) and anti-L-selectin mAb DREG-5640 (Dr T. K. Kishimoto, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT). The antihuman P-selectin mAbs S12 and G1 were prepared and characterized as described previously.33-35 G1, but not S12, blocks binding of P-selectin to leukocytes and PSGL-1.33,36 The antihuman PSGL-1 mAbs PL1 and PL2 were prepared as previously described.37 PL1 blocks PSGL-1 binding to P-selectin and L-selectin but not to E-selectin.8,37,38 PL2 does not inhibit PSGL-1 binding to P-, E-, or L-selectin. The antihuman E-selectin mAbs ES1 and ES2 were produced using previously described methods.39 ES1, but not ES2, blocks E-selectin binding to neutrophils. The antiplatelet IIb integrin antibody Tab was prepared
as described.41,42
Cell isolation Human neutrophils were isolated from heparinized blood by dextran sedimentation, hypotonic lysis, and Ficoll-Hypaque density gradient centrifugation, as previously described.43 HL-60 cells (American Type Culture Collection, Rockville, MD) are a human myeloid cell line that expresses PSGL-1 but little or no L-selectin. The cells were maintained in RPMI 1640 medium supplemented with 100 units/mL penicillin G sodium, 100 units/mL streptomycin sulfate, 1 mmol/L sodium pyruvate, and 15% FBS. Transfected murine L1-2 pre-B cells expressing human P-, E-, or L-selectin44-46 (Dr T. K. Kishimoto, Boehringer Ingelheim Pharmaceuticals) were maintained in RPMI 1640 medium supplemented with 10% heat-inactivated FBS, 2 mmol/L L-glutamine, 0.05 mg/mL gentamicin, 0.055 mmol/L 2-mercaptoethanol, 0.11 mmol/L sodium hypoxanthine, 0.017 mmol/L thymidine, 0.13 mg/mL xanthine, 2.6 µg/mL mycophenolic acid, and 5.4 mmol/L hydrochloric acid (HCl).Preparation of lipid vesicles and lipid bilayers The procedures to produce lipid vesicles and lipid bilayers with an incorporated adhesion molecule were adapted from Mimms et al47 and McConnell et al.48 Egg phosphatidylcholine (5 mg) dissolved in chloroform was dried under nitrogen in a test tube to produce a thin lipid film. Octyl- -D-glucopyranoside (0.03 g) was added to the tube containing
the dried lipid. The lipid film and detergent were dissolved in an
aqueous buffer containing 25 mmol/L Tris HCl
(tris[hydroxymethyl] aminomethane) and 150 mmol/L sodium chloride
(NaCl; pH 7.4). The lipid was dissolved in 300 µL total volume of
buffer that included either purified P-selectin or PSGL-1 to be
incorporated into the vesicles. The solution was added to cellulose
ester dialysis membrane tubing (Spectra/Por 3500 MWCO), and the
detergent was removed by dialysis against 25 mmol/L Tris HCl and 150 mmol/L NaCl (pH 7.4) for 2 days with 2 changes of dialysis buffer.
Lipid bilayers were formed on super-clean glass coverslides (24 mm × 50 mm) that were prepared by boiling the slides in
detergent (Alconox) for 15 minutes, rinsing them with ultrapure water,
and storing the slides in methanol at 4°C. A super-clean coverslide
was coated with a lipid bilayer by placing the glass slide on a
drop of vesicle solution (35-50 µL) for 5 minutes.
Isolation of platelets and PMPs Whole blood was mixed with one-ninth volume of ACD anticoagulant and 0.2 µg/mL PGE1. The blood was centrifuged at 250g for 15 minutes to pellet erythrocytes and leukocytes. The platelet-rich plasma (PRP) was centrifuged at 1250g for 15 minutes to pellet the platelets and produce a platelet-poor plasma (PPP) supernatant. The PPP was centrifuged twice more at 1250g for 15 minutes to remove the remaining platelets. The final supernatant was PPP containing only PMPs (particles less than approximately 1.0 µm) as shown by flow cytometry.Generation of PMPs by calcium ionophore The generation of PMPs by calcium ionophore was adapted from published procedures.49,50 The platelet pellet from 20 mL of blood was resuspended in 6 mL of wash buffer (9 mmol/L Na2EDTA, 26.4 mmol/L Na2HPO4, and 140 mmol/L NaCl; pH 7.4) and centrifuged at 1250g for 15 minutes. This was repeated twice to remove the plasma from the platelets. The final platelet pellet was resuspended in 6-7 mL of 137 mmol/L NaCl, 4 mmol/L KCl, 0.5 mmol/L MgCl2, 0.5 mmol/L Na2HPO4, 5.5 mmol/L glucose, 10 mmol/L HEPES, and 2 mmol/L calcium dichloride (CaCl2; pH 7.4). The calcium ionophore A23187 in DMSO was added to a final concentration of 10 µmol/L, and the platelet suspension was incubated at 37°C for 20 minutes, with occasional stirring. After incubation, the platelets were pelleted by centrifugation at 1250g for 15 minutes. This was repeated to remove all the platelets. The resultant supernatant contained only PMPs in buffer, as shown by flow cytometry.Removal of PMPs by centrifugation PRP, obtained as described above, was stimulated with the calcium ionophore A23187 at a final concentration of 10 µmol/L for 20 minutes at 37°C. The platelet suspension was then centrifuged 3 times at 1250g for 15 minutes each time to generate a PPP that was rich in PMPs. A portion of the PPP was then subjected to high-speed centrifugation, 100 000g, for 2 hours.Generation of PMPs by stored platelets PRP was obtained as described above and incubated at room temperature for 5 days. PMPs were generated spontaneously and detected by flow cytometry. Platelets were removed from the PRP by centrifugation at 1250g for 15 minutes.Detection of PMPs by flow cytometry PMPs were detected and distinguished from platelets by flow cytometry (FACScan, Becton Dickinson, San Jose, CA). The sample to be tested (10 µL) was added to 200 µL buffered saline glucose citrate (BSGC: 1.6 mmol/L KH2PO4, 8.6 mmol/L Na2HPO4, 0.12 mol/L NaCl, 13.6 mmol/L Na3C6H5O7, and 11.1 mmol/L glucose; pH 7.3). A saturating concentration of a fluorescent anti-IIb antibody (2 µg Tab-FITC [fluorescein isothiocyanate]),
which binds to the platelet integrin GP IIb/IIIa, was added and allowed
to incubate at room temperature for 20 minutes. BSGC was added to bring
the total volume up to 2.0 mL. The sample was analyzed on the flow cytometer, and PMPs were identified based on their fluorescence and
forward scatter in relation to a platelet control.29 PMPs were defined as events with elevated levels of fluorescence that were
less than approximately 1 µm in size. As shown in Figure 1, PRP from freshly drawn blood contained
very few PMPs (3%-5% of events). The concentration of PMPs increased
in PRP that had been stored at room temperature for 5 days
(approximately 30% of events). Activating washed platelets with
calcium ionophore produced a plasma-free buffer rich in PMPs (65%-70%
of events). Further quantification of the concentration of PMPs was
attempted using flow cytometry of PMP suspensions prepared with known
concentrations of red blood cells. This method failed to produce
consistent results, possibly because some PMPs, which are capable of
mediating adhesive events, are too small to be detected by flow
cytometry.
HL-60/HL-60 and neutrophil/HL-60 interactions mediated by PMPs The fluid mechanical environment found in the microvasculature was recreated in a parallel plate flow chamber as previously described.51,52 A mAb-coated glass slide was prepared by placing a microscope coverslip on a 40-µL drop of an antihuman CD43 mAb solution (2.0-2.5 µg mAb) for 5 minutes at room temperature before attaching the slide to the flow chamber. HL-60 cells were attached to the antihuman CD43 mAb-coated glass slide by infusing a high concentration of cells (1 × 106/mL) into the flow chamber and allowing the cells to settle onto the surface for 10 minutes. The unbound cells were washed out of the flow chamber by withdrawing HBSS through the system at 1.4 dyne/cm2 for 5 minutes. The bound cells did not roll or detach under the levels of shear stress studied. Typically 20-40 cells remained randomly attached to the surface in a 20× field of view (approximately 0.12 mm2). The HL-60 cells and neutrophils used in the cell-cell interaction assays were washed twice with 5 mmol/L EDTA in HBSS, washed once with HBSS, and resuspended in HBSS/0.6% HSA. PMPs generated by calcium ionophore, PMPs in new PPP, or PMPs in 5-day-old PPP were added at various concentrations to a 6-mL suspension of HL-60 cells or neutrophils and allowed to incubate at room temperature for 15 minutes. The HL-60 cells or neutrophils (final concentration 1 × 106/mL in HBSS/0.6% HSA for all experiments) were withdrawn over the prebound HL-60 cells to determine the effect of PMPs on cell-cell interactions. A cell-cell interaction was defined as a suspended cell binding to a prebound cell for at least 1 video frame (0.033 seconds).Analysis of the shear stress requirement for tether formation Transfected murine L1-2 pre-B cells expressing E-, P-, or L-selectin (1 × 106/mL) in HBSS/0.6% HSA were withdrawn, at various shear stresses, through the flow chamber over HL-60 cells prebound to the antihuman CD43-coated glass slide. The pre-B cells interacted transiently with the prebound cells. The normalized rate of transient cell-cell interactions was determined by counting the number of interactions and dividing by the number of HL-60 cells prebound on the surface, the duration of the experiment, and the flux of pre-B cells through the flow chamber. The number of HL-60 cells in a field of view was always in the range of 20 to 40 cells. We assume that over this narrow range of cell-surface densities, the rate of transient interactions will scale linearly with the density. The transient interaction rate scales linearly with time because the interactions are very short-lived events. Additionally, no change in the rate of transient tether formation was observed during the course of the experiment, which typically lasted 10-15 minutes.
HL-60 cell-cell interactions mediated by PMPs derived from new and old PRP To determine whether PMPs can mediate leukocyte-leukocyte interactions, we used HL-60 cells that express PSGL-1 but lack L-selectin, which has been shown to mediate leukocyte-leukocyte adhesion.8 The surface of the flow chamber consisted of HL-60 cells prebound to an antihuman CD43 mAb-coated glass slide. This surface was used to study leukocyte-leukocyte interactions in a system where the only source of P-selectin was the PMPs. Washed HL-60 cells incubated with various concentrations of PMPs were withdrawn over the adherent HL-60 cells at 0.4 dyne/cm2. The number of cell-cell interactions was counted and normalized by the number of cells on the surface and the duration of the experiment. A cell-cell interaction was defined as a flowing cell binding to an attached cell for at least 1 video frame. The cell-cell interactions were transient: A flowing cell would attach to a bound cell briefly (less than 2-3 seconds) then release back into the flowing stream. In the absence of PMPs, very few flowing HL-60 cells tethered to adherent HL-60 cells. The addition of 1-4 mL PMP suspension in new PPP had little effect on the rate of cell-cell interaction (Figure 2). This corresponded to a final PMP concentration that was approximately one-half to twice the normal concentration in blood. The PPP from aged PRP contained approximately 10 times the normal concentration of PMPs. Increasing concentrations of these PMPs significantly enhanced tethering of flowing HL-60 cells to adherent HL-60 cells (P < .05). At higher concentrations of PMPs than illustrated in Figure 2, the HL-60 cells formed large aggregates (typically 10 to more than 30 cells), thereby decreasing their ability to tether to adherent HL-60 cells at the shear rate examined.
HL-60 cell-cell interactions mediated by PMPs generated by calcium ionophore We investigated the possibility that a plasma component was required for the observed cell-cell interactions by generating microparticles from washed platelets with the ionophore A23187. As illustrated in Figure 3, serial increases in the concentration of these PMPs also significantly increased the number of cell-cell interactions (P < .05 for more than 0.2 mL PMP). As occurred with the microparticles generated from aged PRP, high concentrations of washed PMPs caused significant HL-60 cell aggregation, thereby decreasing transient tethering to adherent HL-60 cells.
HL-60 cell-cell interactions mediated by PMPs require P-selectin and PSGL-1 HL-60 cell-cell interaction assays with PMPs generated by calcium ionophore from washed platelets were performed in the presence of blocking and nonblocking antibodies to determine the specificity of the interactions. The nonblocking anti-P-selectin antibody S12 and the nonblocking anti-PSGL-1 antibody PL2 did not significantly inhibit PMP-enhanced HL-60 cell-cell interactions (Figure 4). However, the anti-P-selectin blocking antibody G1 or the anti-PSGL-1 blocking antibody PL1 eliminated the HL-60 cell-cell interactions (Figure 4). Therefore, P-selectin and PSGL-1 mediated the HL-60 cell-cell interactions produced by PMPs.
Neutrophil/HL-60 cell-cell interactions mediated by PMPs Unlike HL-60 cells, neutrophils express PSGL-1 as well as L-selectin, which binds to PSGL-1. Neutrophils (1 × 106/mL) in HBSS/0.6% HSA were perfused over HL-60 cells prebound to antihuman CD43 mAb. Cell-cell interactions between flowing neutrophils and adherent HL-60 cells occurred readily without the addition of PMPs (Figure 5A). These cell-cell interactions were mediated by L-selectin since they were largely eliminated in the presence of the blocking anti-L-selectin mAb DREG-56 (P < .01; Figure 5A). In the presence of DREG-56, the addition of PMPs significantly increased the rate of neutrophil interactions with bound HL-60 cells (P < .01; Figure 5A). Increasing the concentration of PMPs (1.5 mL) increased the number of cell-cell interactions (data not shown).
Differential effect of shear stress on bond formation through selectins L-selectin-ligand bonds dissociate much faster than P-selectin-ligand bonds. One consequence of this is that there is a much more pronounced threshold shear stress required to support L-selectin-mediated cell tethering and rolling.12,13,53,54 We confirmed this finding in a system in which murine pre-B cells expressing L-, E-, or P-selectin were perfused over prebound PSGL-1-expressing HL-60 cells at different shear stresses. Transient tethers of L-selectin-expressing cells reached a maximum between 1.0 and 1.4 dyne/cm2. At shear stresses less than 1.0 dyne/cm2 or greater than approximately 2.0 dyne/cm2, the rate of transient cell-cell interactions decreased dramatically (Figure 6). Transient tethers of pre-B cells expressing P- or E-selectin continued to increase at shear stresses as low as 0.4 dyne/cm2 (Figure 6). The shear dependence on tether formation between L-selectin and PSGL-1 was also obtained when neutrophils were withdrawn over prebound HL-60 cells or over a phospholipid bilayer containing purified PSGL-1 (data not shown).
PMP-mediated cell-cell interactions at low shear stresses We next determined if PMPs could enhance accumulation of neutrophils on a selectin substrate in the presence of shear stress in addition to the increased rate of transient tether formation demonstrated above. Neutrophils (1 × 106/mL) in HBSS/0.6% HSA were withdrawn over a planar lipid bilayer containing P-selectin, and the number of cells that accumulated on the surface was determined as a function of time (Figure 7). Most neutrophils withdrawn over the P-selectin bilayer at 1.4 dyne/cm2 accumulated on the surface in lines or strings as a consequence of initial binding followed by L-selectin-mediated cell-cell interactions. Blocking these cell-cell interactions with the anti-L-selectin mAb DREG-56 significantly reduced accumulation on the P-selectin substrate by approximately 70% (P < .01; Figure 7). Accumulation of neutrophils on the P-selectin bilayer at 0.4 dyne/cm2 occurred largely through attachment of cells directly to the surface (primary attachment) and only occasionally through cell-cell interactions (secondary attachment). The increased ability of cells to bind directly to P-selectin on the surface under low shear stress did not offset the overall reduction in accumulation because of less efficient L-selectin-mediated cell-cell interactions. Consequently, neutrophil accumulation at 0.4 dyne/cm2 was significantly reduced. In the presence of PMPs, secondary attachment of neutrophils to the surface occurred at 0.4 dyne/cm2, and accumulation of neutrophils was significantly increased (P < .05; Figure 7).
PMPs support cell-cell interactions at lower shear stress HL-60 cells incubated with various concentrations of PMPs were withdrawn over prebound HL-60 cells. The HL-60 cell suspension was perfused over a range of shear stresses to determine the effect of increased PMP concentrations on the production of cell-cell interactions at both higher and lower shear stresses. PMPs were able to support cell-cell interactions at shear stresses as low as 0.15 dyne/cm2 (Figure 8). Increasing the concentration of PMPs significantly increased the rate of cell-cell interactions (P < 0.05). These P-selectin-mediated interactions may occur at even lower shear stresses, but we were not able to determine a lower shear stress limit for PMP-mediated cell-cell interactions due to increasing nonspecific interactions.
PMPs released from activated platelets express functional adhesion receptors including P-selectin. Plasma PMP concentrations are elevated in patients with thrombotic and inflammatory disorders, and the role of PMPs in enhancing leukocyte aggregation and adhesion to vascular surfaces has not been addressed. We have shown that PMPs can mediate leukocyte-leukocyte interactions and that these attachments lead to increased accumulation of leukocytes on a P-selectin surface. Since PMPs use P-selectin to bridge leukocytes, they occur at lower shear stresses than leukocyte-leukocyte interactions mediated by L-selectin.
The authors thank George Dale for reviewing the manuscript and Laura Worthen for technical assistance.
Submitted May 11, 1999; accepted October 7, 1999.
Supported by grant HN6-017 from the Oklahoma Center for Advancement of Science and Technology, Oklahoma City, Oklahoma, and by grant HL54304 from the National Institutes of Health, Bethesda, MD.
Reprints: Matthias U. Nollert, University of Oklahoma, School of Chemical Engineering and Materials Science, 100 E. Boyd, Energy Center, Room T-335, Norman, OK 73019; email: nollert{at}ou.edu.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
1.
Kansas GS.
Selectins and their ligands: current concepts and controversies.
Blood.
1996;88:3259 2. Ley K, Tedder TF. Leukocyte interactions with vascular endothelium. New insights into selectin-mediated attachment and rolling. J Immunol. 1995;155:525[Abstract]. 3. McEver RP. Selectin-carbohydrate interactions during inflammation and metastasis. Glycoconj J. 1997;14:585[Medline] [Order article via Infotrieve].
4.
Alon R, Kassner PD, Carr MW, Finger EB, Hemler ME, Springer TA.
The integrin VLA-4 supports tethering and rolling in flow on VCAM-1.
J Cell Biol.
1995;128:1243
5.
Johnston B, Issekutz TB, Kubes P.
The alpha 4-integrin supports leukocyte rolling and adhesion in chronically inflamed postcapillary venules in vivo.
J Exp Med.
1996;183:1995 6. McEver RP, Cummings RD. Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest. 1997;100:485[Medline] [Order article via Infotrieve].
7.
Spertini O, Cordey AS, Monai N, Giuffre L, Schapira M.
P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+ hematopoietic progenitor cells.
J Cell Biol.
1996;135:523 8. Walcheck B, Moore KL, McEver RP, Kishimoto TK. Neutrophil-neutrophil interactions under hydrodynamic shear stress involve L-selectin and PSGL-1. A mechanism that amplifies initial leukocyte accumulation of P-selectin in vitro. J Clin Invest. 1996;98:1081[Medline] [Order article via Infotrieve]. 9. Ramos CL, Smith MJ, Snapp KR, et al. Functional characterization of L-selectin ligands on human neutrophils and leukemia cell lines: evidence for mucin-like ligand activity distinct from P-selectin glycoprotein ligand-1. Blood. 1998;9:1067.
10.
Bargatze RF, Kurk S, Butcher EC, Jutila MA.
Neutrophils roll on adherent neutrophils bound to cytokine-induced endothelial cells via L-selectin on the rolling cells.
J Exp Med.
1994;180:1785
11.
Alon R, Fuhlbrigge RC, Finger EB, Springer TA.
Interactions through L-selectin between leukocytes and adherent leukocytes nucleate rolling adhesions on selectins and VCAM-1 in shear flow.
J Cell Biol.
1996;135:849
12.
Alon R, Chen S, Puri KD, Finger EB, Springer TA.
The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling.
J Cell Biol.
1997;138:1169 13. Finger EB, Puri KD, Alon R, Lawrence MB, von Andrian UH, Springer TA. Adhesion through L-selectin requires a threshold hydrodynamic shear. Nature. 1996;379:266[Medline] [Order article via Infotrieve].
14.
Buttrum SM, Hatton R, Nash GB.
Selectin-mediated rolling of neutrophils on immobilized platelets.
Blood.
1993;82:1165
15.
Diacovo TG, Roth SJ, Buccola JM, Bainton DF, Springer TA.
Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18.
Blood.
1996;88:146
16.
Kuijper PH, Gallardo Torres HI, van der Linden JA, et al.
Platelet-dependent primary hemostasis promotes selectin- and integrin-mediated neutrophil adhesion to damaged endothelium under flow conditions.
Blood.
1996;87:3271
17.
Konstantopoulos K, Neelamegham S, Burns AR, et al.
Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin.
Circulation.
1998;98:873 18. Ostrovsky L, King AJ, Bond S, et al. A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process. Blood. 1998;9:3028. 19. Bazzoni G, Dejana E, Del Maschio A. Platelet-neutrophil interactions. Possible relevance in the pathogenesis of thrombosis and inflammation. Haematologica. 1991;76:491[Medline] [Order article via Infotrieve].
20.
Jungi TW, Spycher MO, Nydegger UE, Barandun S.
Platelet-leukocyte interaction: selective binding of thrombin-stimulated platelets to human monocytes, polymorphonuclear leukocytes, and related cell lines.
Blood.
1986;67:629
21.
Yeo EL, Sheppard JA, Feuerstein IA.
Role of P-selectin and leukocyte activation in polymorphonuclear cell adhesion to surface adherent activated platelets under physiologic shear conditions (an injury vessel wall model).
Blood.
1994;83:2498 22. Palabrica T, Lobb R, Furie BC, et al. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature. 1992;359:848[Medline] [Order article via Infotrieve]. 23. George JN, Pickett EB, Saucerman S, et al. Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery. J Clin Invest. 1986;78:340.
24.
Abrams CS, Ellison N, Budzynski AZ, Shattil SJ.
Direct detection of activated platelets and platelet-derived microparticles in humans.
Blood.
1990;75:128 25. Nomura S, Komiyama Y, Matsuura E, et al. Participation of alpha IIb beta 3 in platelet microparticle generation by collagen plus thrombin. Haemostasis. 1996;26:31[Medline] [Order article via Infotrieve]. 26. Nomura S, Yanabu M, Miyake T, et al. Relationship of microparticles with beta 2-glycoprotein I and P-selectin positivity to anticardiolipin antibodies in immune thrombocytopenic purpura. Ann Hematol. 1995;70:25[Medline] [Order article via Infotrieve]. 27. Pasquet JM, Toti F, Nurden AT, Dachary-Prigent J. Procoagulant activity and active calpain in platelet-derived microparticles. Thromb Res. 1996;82:509[Medline] [Order article via Infotrieve]. 28. Sandberg H, Bode AP, Dombrose FA, Hoechli M, Lentz BR. Expression of coagulant activity in human platelets: release of membranous vesicles providing platelet factor 1 and platelet factor 3. Thromb Res. 1985;39:63[Medline] [Order article via Infotrieve].
29.
Sims PJ, Faioni EM, Wiedmer T, Shattil SJ.
Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity.
J Biol Chem.
1988;263:18,205 30. Jy W, Mao WW, Horstman L, Tao J, Ahn YS. PMPs bind, activate and aggregate neutrophils in vitro. Blood Cells Mol Dis. 1995;21:217[Medline] [Order article via Infotrieve]. 31. Moore KL. Purification of P-selectin (CD62P) from human platelets. J Tissue Culture Methods. 1994;16:1.
32.
Moore KL, Eaton SF, Lyons DE, Lichenstein HS, Cummings RD, McEver RP.
The P-selectin glycoprotein ligand from human neutrophils displays sialylated, fucosylated, O-linked poly-N-acetyllactosamine.
J Biol Chem.
1994;269:23,318 33. Geng JG, Bevilacqua MP, Moore KL, et al. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990;343:757[Medline] [Order article via Infotrieve].
34.
Johnston GI, Kurosky A, McEver RP.
Structural and biosynthetic studies of the granule membrane protein, GMP-140, from human platelets and endothelial cells.
J Biol Chem.
1989;264:1816
35.
McEver RP, Martin MN.
A monoclonal antibody to a membrane glycoprotein binds only to activated platelets.
J Biol Chem.
1984;259:9799
36.
Hamburger SA, McEver RP.
GMP-140 mediates adhesion of stimulated platelets to neutrophils.
Blood.
1990;75:550
37.
Moore KL, Patel KD, Bruehl RE, et al.
P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin.
J Cell Biol.
1995;128:661 38. Patel KD, McEver RP. Comparison of tethering and rolling of eosinophils and neutrophils through selectins and P-selectin glycoprotein ligand-1. J Immunol. 1997;159:4555[Abstract]. 39. Patel KD, Moore KL, Nollert MU, McEver RP. Neutrophils use both shared and distinct mechanisms to adhere to selectins under static and flow conditions. J Clin Invest. 1995;96:1887.
40.
Kishimoto TK, Jutila MA, Butcher EC.
Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule.
Proc Natl Acad Sci U S A.
1990;87:2244 41. McEver RP, Baenziger NL, Majerus PW. Isolation and quantitation of the platelet membrane glycoprotein deficient in thrombasthenia using a monoclonal hybridoma antibody. J Clin Invest. 1980;66:1311.
42.
McEver RP, Bennett EM, Martin MN.
Identification of two structurally and functionally distinct sites on human platelet membrane glycoprotein IIb-IIIa using monoclonal antibodies.
J Biol Chem.
1983;258:5269 43. Zimmerman GA, McIntyre TM, Prescott SM. Thrombin stimulates the adherence of neutrophils to human endothelial cells in vitro. J Clin Invest. 1985;76:2235.
44.
Liu W, Ramachandran V, Kang J, Kishimoto TK, Cummings RD, McEver RP.
Identification of N-terminal residues on P-selectin glycoprotein ligand-1 required for binding to P-selectin.
J Biol Chem.
1998;273:7078 45. von Andrian UH, Hasslen SR, Nelson RD, Erlandsen SL, Butcher EC. A central role for microvillous receptor presentation in leukocyte adhesion under flow. Cell 1995;82:989[Medline] [Order article via Infotrieve]. 46. Diacovo TG, Puri KD, Warnock RA, Springer TA, von Andrian UH. Platelet-mediated lymphocyte delivery to high endothelial venules. Science. 1996;273:252[Abstract]. 47. Mimms LT, Zampighi G, Nozaki Y, Tanford C, Reynolds JA. Phospholipis vesicle formation and transmembrane protein incorporation using octly glucoside. Biochemistry. 1991;20:833. 48. McConnell HM, Watts TH, Weis RM, Brian AA. Supported planar membranes in studies of cell-cell recognition in the immune system. Biochim Biophys Acta. 1986;864:95[Medline] [Order article via Infotrieve]. 49. Nomura S, Suzuki M, Katsura K, et al. Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus. Atherosclerosis. 1995;116:235[Medline] [Order article via Infotrieve]. 50. Pasquet JM, Dachary-Prigent J, Nurden AT. Calcium influx is a determining factor of calpain activation and microparticle formation in platelets. Eur J Biochem. 1996;239:647[Medline] [Order article via Infotrieve]. 51. Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991;65:859[Medline] [Order article via Infotrieve]. 52. Lawrence MB, Springer TA. Neutrophils roll on E-selectin. J Immunol. 1993;151:6338[Abstract].
53.
Lawrence MB, Kansas GS, Kunkel EJ, Ley K.
Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L, P, E) [published correction appears in J Cell Biol. 1997;137:261].
J Cell Biol.
1997;136:717
54.
Alon R, Chen S, Fuhlbrigge R, Puri KD, Springer TA.
The kinetics and shear threshold of transient and rolling interactions of L-selectin with its ligand on leukocytes.
Proc Natl Acad Sci U S A.
1998;95:11,631
55.
Diacovo TG, Catalina MD, Siegelman MH, von Andrian UH.
Circulating activated platelets reconstitute lymphocyte homing and immunity in L-selectin-deficient mice.
J Exp Med.
1998;187:197
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|
 |
|
  A. C. Vedder, E. Biro, J. M. F. G. Aerts, R. Nieuwland, G. Sturk, and C. E. M. Hollak Plasma markers of coagulation and endothelial activation in Fabry disease: impact of renal impairment Nephrol. Dial. Transplant., October 1, 2009; 24(10): 3074 - 3081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Dasgupta, H. Abdel-Monem, P. Niravath, A. Le, R. V. Bellera, K. Langlois, S. Nagata, R. E. Rumbaut, and P. Thiagarajan Lactadherin and clearance of platelet-derived microvesicles Blood, February 5, 2009; 113(6): 1332 - 1339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Montecucco and F. Mach Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthritis and atherosclerosis Rheumatology, January 1, 2009; 48(1): 11 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Erdbruegger, M. Grossheim, B. Hertel, K. Wyss, T. Kirsch, A. Woywodt, H. Haller, and M. Haubitz Diagnostic role of endothelial microparticles in vasculitis Rheumatology, December 1, 2008; 47(12): 1820 - 1825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Xiao, G. P. Visentin, K. M. Dayananda, and S. Neelamegham Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion Blood, August 15, 2008; 112(4): 1091 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Sprague, B. D. Elzey, S. A. Crist, T. J. Waldschmidt, R. J. Jensen, and T. L. Ratliff Platelet-mediated modulation of adaptive immunity: unique delivery of CD154 signal by platelet-derived membrane vesicles Blood, May 15, 2008; 111(10): 5028 - 5036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Li Platelet-lymphocyte cross-talk J. Leukoc. Biol., May 1, 2008; 83(5): 1069 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nolan, R. Dixon, K. Norman, P. Hellewell, and V. Ridger Nitric Oxide Regulates Neutrophil Migration through Microparticle Formation Am. J. Pathol., January 1, 2008; 172(1): 265 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Salanova, M. Choi, S. Rolle, M. Wellner, F. C. Luft, and R. Kettritz beta2-Integrins and Acquired Glycoprotein IIb/IIIa (GPIIb/IIIa) Receptors Cooperate in NF-{kappa}B Activation of Human Neutrophils J. Biol. Chem., September 21, 2007; 282(38): 27960 - 27969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Othman, A. Labelle, I. Mazzetti, H. S. Elbatarny, and D. Lillicrap Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance Blood, April 1, 2007; 109(7): 2832 - 2839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Morel, F. Toti, B. Hugel, B. Bakouboula, L. Camoin-Jau, F. Dignat-George, and J.-M. Freyssinet Procoagulant Microparticles: Disrupting the Vascular Homeostasis Equation? Arterioscler Thromb Vasc Biol, December 1, 2006; 26(12): 2594 - 2604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ichimura, K. Parthasarathi, A. C. Issekutz, and J. Bhattacharya Pressure-induced leukocyte margination in lung postcapillary venules Am J Physiol Lung Cell Mol Physiol, September 1, 2005; 289(3): L407 - L412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Mause, P. von Hundelshausen, A. Zernecke, R. R. Koenen, and C. Weber Platelet Microparticles: A Transcellular Delivery System for RANTES Promoting Monocyte Recruitment on Endothelium Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1512 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Burdick and K. Konstantopoulos Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow Am J Physiol Cell Physiol, August 1, 2004; 287(2): C539 - C547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hagihara, A. Higuchi, N. Tamura, Y. Ueda, K. Hirabayashi, Y. Ikeda, S. Kato, S. Sakamoto, T. Hotta, S. Handa, et al. Platelets, after Exposure to a High Shear Stress, Induce IL-10-Producing, Mature Dendritic Cells In Vitro J. Immunol., May 1, 2004; 172(9): 5297 - 5303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. VanWijk, E. VanBavel, A. Sturk, and R. Nieuwland Microparticles in cardiovascular diseases Cardiovasc Res, August 1, 2003; 59(2): 277 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Burger and D. D. Wagner Platelet P-selectin facilitates atherosclerotic lesion development Blood, April 1, 2003; 101(7): 2661 - 2666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Preston, W. Jy, J. J. Jimenez, L. M. Mauro, L. L. Horstman, M. Valle, G. Aime, and Y. S. Ahn Effects of Severe Hypertension on Endothelial and Platelet Microparticles Hypertension, February 1, 2003; 41(2): 211 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kanamori, N. Kojima, K. Uchimura, T. Muramatsu, T. Tamatani, M. C. Berndt, G. S. Kansas, and R. Kannagi Distinct Sulfation Requirements of Selectins Disclosed Using Cells That Support Rolling Mediated by All Three Selectins under Shear Flow. L-SELECTIN PREFERS CARBOHYDRATE 6-SULFATION TO TYROSINE SULFATION, WHEREAS P-SELECTIN DOES NOT J. Biol. Chem., August 30, 2002; 277(36): 32578 - 32586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huber, A. Vales, G. Mitulovic, M. Blumer, R. Schmid, J. L. Witztum, B. R. Binder, and N. Leitinger Oxidized Membrane Vesicles and Blebs From Apoptotic Cells Contain Biologically Active Oxidized Phospholipids That Induce Monocyte-Endothelial Interactions Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 101 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Janowska-Wieczorek, M. Majka, J. Kijowski, M. Baj-Krzyworzeka, R. Reca, A. R. Turner, J. Ratajczak, S. G. Emerson, M. A. Kowalska, and M. Z. Ratajczak Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment Blood, November 15, 2001; 98(10): 3143 - 3149. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2000 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
Top
Abstract
Introduction
IIb antibody Tab-FITC) versus forward
scatter intensity of platelets and PMPs.
The following are depicted: (A) PRP from freshly drawn blood; (B) PPP
that has been centrifuged 3 times at 1250g; (C) PRP from blood that has
been stored for 5 days; and (D) PPP from stored blood. The vertical
gate was drawn to identify particles less than approximately 1 µm in
size, and the horizontal gate was drawn at a fluorescence intensity
above the background level. Events were collected for 90 seconds for
all cases.
