From the Cox Laboratory for Biomedical Engineering, Institute of
Biosciences and Bioengineering, Rice University, Houston, Tex (K.K., J.D.H.,
L.V.M.); Speros P. Martel Section of Leukocyte Biology, Department of
Pediatrics, Baylor College of Medicine, Houston, Tex (S.N., A.R.B., E.H.,
C.W.S., S.I.S.); Northwestern Medical School, Chicago, Ill (G.S.K., K.R.S.);
and Protein Design Labs Inc, Mountain View, Calif (E.L.B.)
Correspondence to Scott I. Simon, PhD, Children's Nutrition Research Center, 1100 Bates St, Room 6014, Houston, TX 77030-2600. E-mail ssimon{at}bcm.tmc.edu
Background—After activation,
platelets adhere to neutrophils via P-selectin and
ß2-integrin. The molecular mechanisms and adhesion events
in whole blood exposed to venous levels of hydrodynamic shear in the
absence of exogenous activation remain unknown.
Methods and Results—Whole blood was sheared at
Conclusions—The results are consistent with a model in
which venous levels of shear support platelet adherence to
neutrophils via P-selectin binding PSGL-1. This interaction alone is
sufficient to mediate neutrophil aggregation. Abrogation of
platelet adhesion and aggregation requires blocking Mac-1 in
addition to PSGL-1 or P-selectin. The described mechanisms are likely
of key importance in the pathogenesis and progression of thrombotic
disorders that are exacerbated by leukocyte-platelet aggregation.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Venous Levels of Shear Support Neutrophil-Platelet Adhesion and Neutrophil Aggregation in Blood via P-Selectin and ß2-Integrin
100
s-1. The kinetics of neutrophil-platelet adhesion and
neutrophil aggregation were measured in real time by flow cytometry.
P-selectin was upregulated to the platelet surface in response to
shear and was the primary factor mediating neutrophil-platelet
adhesion. The extent of neutrophil aggregation increased linearly with
platelet adhesion to neutrophils. Blocking either P-selectin, its
glycoprotein ligand PSGL-1, or both
simultaneously by preincubation with a monoclonal
antibody resulted in equivalent inhibition of
neutrophil-platelet adhesion (30%) and neutrophil aggregation
(70%). The residual amount of neutrophil adhesion was blocked with
anti-CD11b/CD18. Treatment of blood with prostacyclin analogue ZK36374,
which raises cAMP levels in platelets, blocked P-selectin
upregulation and neutrophil aggregation to baseline. Complete
abrogation of platelet-neutrophil adhesion required both ZK36374
and anti-CD18. Electron microscopic observations of fixed blood
specimens revealed that platelets augmented neutrophil aggregation
both by forming bridges between neutrophils and through
contact-mediated activation.
Key Words: blood cells • neutrophils • platelets • glycoproteins • integrins
This article has been cited by other articles:
 |
|
 |
|
  J. M. van Gils, J. J. Zwaginga, and P. L. Hordijk Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases J. Leukoc. Biol., February 1, 2009; 85(2): 195 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Oh and S. L. Diamond Ethanol Enhances Neutrophil Membrane Tether Growth and Slows Rolling on P-Selectin but Reduces Capture from Flow and Firm Arrest on IL-1-Treated Endothelium J. Immunol., August 15, 2008; 181(4): 2472 - 2482. [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]
|
|
|
|
|
|
N. Li Platelet-lymphocyte cross-talk J. Leukoc. Biol., May 1, 2008; 83(5): 1069 - 1078. [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]
|
|
|
|
 |
|
 H. F. Langer, K. Daub, G. Braun, T. Schonberger, A. E. May, M. Schaller, G. M. Stein, K. Stellos, A. Bueltmann, D. Siegel-Axel, et al. Platelets Recruit Human Dendritic Cells Via Mac-1/JAM-C Interaction and Modulate Dendritic Cell Function In Vitro Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1463 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Thom, V. M. Bhopale, S.-T. Han, J. M. Clark, and K. R. Hardy Intravascular Neutrophil Activation Due to Carbon Monoxide Poisoning Am. J. Respir. Crit. Care Med., December 1, 2006; 174(11): 1239 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lu, Y. Chen, YinHuang, W. Li, and M. Jiang Venous Hypertension Induces Increased Platelet Reactivity and Accumulation in Patients with Chronic Venous Insufficiency Angiology, May 1, 2006; 57(3): 321 - 329. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Ferenc and F.-J. Neumann Efficacy of primary PCI: the microvessel perspective Eur. Heart J. Suppl., October 1, 2005; 7(suppl_I): I4 - I9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Ritter, K. M. Stempel, B. M. Coull, and P. F. McDonagh Leukocyte-Platelet Aggregates in Rat Peripheral Blood After Ischemic Stroke and Reperfusion Biol Res Nurs, April 1, 2005; 6(4): 281 - 288. [Abstract] [PDF]
|
|
|
|
|
|
S. C. Pitchford, S. Momi, S. Giannini, L. Casali, D. Spina, C. P. Page, and P. Gresele Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation Blood, March 1, 2005; 105(5): 2074 - 2081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Merten, C. Beythien, K. Gutensohn, P. Kuhnl, T. Meinertz, and P. Thiagarajan Sulfatides Activate Platelets Through P-Selectin and Enhance Platelet and Platelet-Leukocyte Aggregation Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 258 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Khreiss, L. Jozsef, L. A. Potempa, and J. G. Filep Opposing Effects of C-Reactive Protein Isoforms on Shear-Induced Neutrophil-Platelet Adhesion and Neutrophil Aggregation in Whole Blood Circulation, October 26, 2004; 110(17): 2713 - 2720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pawar, P. K. Shin, S. A. Mousa, J. M. Ross, and K. Konstantopoulos Fluid Shear Regulates the Kinetics and Receptor Specificity of Staphylococcus aureus Binding to Activated Platelets J. Immunol., July 15, 2004; 173(2): 1258 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wei, G. Tai, Y. Gao, N. Li, B. Huang, Y. Zhou, S. Hao, and X. Zeng Modified Heparin Inhibits P-selectin-mediated Cell Adhesion of Human Colon Carcinoma Cells to Immobilized Platelets under Dynamic Flow Conditions J. Biol. Chem., July 9, 2004; 279(28): 29202 - 29210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Cooper, J. Russell, K. D. Chitman, M. C. Williams, R. E. Wolf, and D. N. Granger Leukocyte dependence of platelet adhesion in postcapillary venules Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1895 - H1900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Wagner and P. C. Burger Platelets in Inflammation and Thrombosis Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2131 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fukuda and G. W. Schmid-Schonbein Regulation of CD18 expression on neutrophils in response to fluid shear stress PNAS, November 11, 2003; 100(23): 13152 - 13157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. J. T. McCarty, N. Tien, B. S. Bochner, and K. Konstantopoulos Exogenous eosinophil activation converts PSGL-1-dependent binding to CD18-dependent stable adhesion to platelets in shear flow Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1223 - C1234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Russell, D. Cooper, A. Tailor, K. Y. Stokes, and D. N. Granger Low venular shear rates promote leukocyte-dependent recruitment of adherent platelets Am J Physiol Gastrointest Liver Physiol, January 1, 2003; 284(1): G123 - G129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jadhav and K. Konstantopoulos Fluid shear- and time-dependent modulation of molecular interactions between PMNs and colon carcinomas Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1133 - C1143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Kaneider, P. Egger, S. Dunzendorfer, and C. J. Wiedermann Rho-GTPase-Dependent Platelet-Neutrophil Interaction Affected by HMG-CoA Reductase Inhibition With Altered Adenosine Nucleotide Release and Function Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 1029 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jadhav, B. S. Bochner, and K. Konstantopoulos Hydrodynamic Shear Regulates the Kinetics and Receptor Specificity of Polymorphonuclear Leukocyte-Colon Carcinoma Cell Adhesive Interactions J. Immunol., November 15, 2001; 167(10): 5986 - 5993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Eppihimer and R. G. Schaub P-Selectin-Dependent Inhibition of Thrombosis During Venous Stasis Arterioscler. Thromb. Vasc. Biol., November 1, 2000; 20(11): 2483 - 2488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Merten, T. Chow, J. D. Hellums, and P. Thiagarajan A New Role for P-Selectin in Shear-Induced Platelet Aggregation Circulation, October 24, 2000; 102(17): 2045 - 2050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. T. McCarty, S. A. Mousa, P. F. Bray, and K. Konstantopoulos Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions Blood, September 1, 2000; 96(5): 1789 - 1797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Neelamegham, A. D. Taylor, H. Shankaran, C. W. Smith, and S. I. Simon Shear and Time-Dependent Changes in Mac-1, LFA-1, and ICAM-3 Binding Regulate Neutrophil Homotypic Adhesion J. Immunol., April 1, 2000; 164(7): 3798 - 3805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Fredrickson, N. A. Turner, N. S. Kleiman, N. Graziadei, K. Maresh, M. A. Mascelli, M. B. Effron, and L. V. McIntire Effects of Abciximab, Ticlopidine, and Combined Abciximab/Ticlopidine Therapy on Platelet and Leukocyte Function in Patients Undergoing Coronary Angioplasty Circulation, March 14, 2000; 101(10): 1122 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Forlow, R. P. McEver, and M. U. Nollert Leukocyte-leukocyte interactions mediated by platelet microparticles under flow Blood, February 15, 2000; 95(4): 1317 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Hentzen, S. Neelamegham, G. S. Kansas, J. A. Benanti, L. V. McIntire, C. W. Smith, and S. I. Simon Sequential binding of CD11a/CD18 and CD11b/CD18 defines neutrophil capture and stable adhesion to intercellular adhesion molecule-1 Blood, February 1, 2000; 95(3): 911 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-J. Neumann, D. Zohlnhofer, L. Fakhoury, I. Ott, M. Gawaz, and A. Schomig Effect of glycoprotein IIb/IIIa receptor blockade on platelet-leukocyte interaction and surface expression of the leukocyte integrin Mac-1 in acute myocardial infarction J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1420 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S. Olson, K. Singbartl, and K. Ley L-selectin is required for fMLP- but not C5a-induced margination of neutrophils in pulmonary circulation Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1245 - R1252. [Abstract] [Full Text] [PDF]
|
|