Surface-Secreted von Willebrand Factor Mediates Aggregation of ADP-Activated Platelets at Moderate Shear Stress: Facilitated by GPIb but Controlled by GPIIb-IIIa

M M Frojmovic; A Kasirer-Friede; H L Goldsmith; E A Brown

doi:10.1055/s-0038-1656007

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1997; 77(03): 568-576
DOI: 10.1055/s-0038-1656007

Platelets

Schattauer GmbH Stuttgart

Surface-Secreted von Willebrand Factor Mediates Aggregation of ADP-Activated Platelets at Moderate Shear Stress: Facilitated by GPIb but Controlled by GPIIb-IIIa

M M Frojmovic

¹The Departments of Physiology and Medicine, McGill University Medical Clinic, Montreal General Hospital, Montreal, Canada

,

A Kasirer-Friede

¹The Departments of Physiology and Medicine, McGill University Medical Clinic, Montreal General Hospital, Montreal, Canada

,

H L Goldsmith

¹The Departments of Physiology and Medicine, McGill University Medical Clinic, Montreal General Hospital, Montreal, Canada

²The Departments of Physiology and Medicine, McGill University Medical Clinic, Montreal General Hospital, Montreal, Canada

,

E A Brown

¹The Departments of Physiology and Medicine, McGill University Medical Clinic, Montreal General Hospital, Montreal, Canada

› Institutsangaben

Abstract

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Summary

We previously showed that ADP activation of washed human platelets in plasma-free suspensions supports aggregation at moderate shear stress (0.4-1.6 Nm^-2) in Poiseuille flow. Although most activated platelets expressed maximal fibrinogen-occupied GPIIb-IIIa receptors, aggregation appeared to be independent of bound fibrinogen, but blocked by the hexapeptide GRGDSP. Here, we tested the hypothesis that von Willebrand factor (vWF) secreted and expressed on activated platelets mediates aggregation at moderate shear rates from 300 to 1000 s^_1 corresponding to shear stresses from 0.3 to 1.1 Nm^-2. Relatively unactivated platelets (<15% expressing prebound fibrinogen) were prepared from acidified citrated platelet rich plasma (cPRP) by single centrifugation with 50 nM stable prostacyclin derivative ZK 36374 and resuspended in Tyrodes-albumin at 5 X 10⁴ cells ε^_1. Flow cytometric measurements with monoclonal antibody (mAb) 2.2.9 reporting on surface-bound vWF, and with mAb S12 reporting on a-granule secreted P-selectin, showed that 65% and 80%, respectively, of all platelets were maximally activated with respect to maximal secretion and surface expression of these proteins. “Resting” washed platelets exhibited both surface-bound vWF and significant P-selectin secretion. We showed that mAbs 6D1 and NMC4, respectively blocking the adhesive domains on the GPIb receptor recognizing vWF, and on the vWF molecule recognizing the GPIb receptor, partially inhibited ADP-induced aggregation under shear in Couette flow, the degree of inhibition increasing with increasing shear stress. In contrast, mAb 10E5, blocking the vWF binding domain on GPIIb-IIIa, essentially blocked all aggregation at the shear rates tested. We conclude that vWF, expressed on ADP-activated platelets, is at least the predominant cross-bridging molecule mediating aggregation at moderate shear stress. There is an absolute requirement for free activated GPIIb-IIIa receptors, postulated to interact with platelet-secreted, surface bound vWF. The GPIb-vWF cross-bridging reaction plays a facilitative role becoming increasingly important with increasing shear stress. Since aurin tricarboxylic acid, which blocks the GPIb binding domain on vWF, was also found to completely block aggregation in Poiseuille flow, we conclude that it too affects the GPIIb-IIIa interaction.

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Referenzen

References
1 Goldsmith HL, Frojmovic MM, Braovac S, McIntosh F, Wong T. Adenosine diphosphate-induced aggregation of human platelets in flow through tubes: III. Shear and extrinsic fibrinogen-dependent effects. Thromb Haemost 1994; 71: 0078-0090
2 Timmons S, Hawiger J. von Willebrand factor can substitute for plasma fibrinogen in ADP-induced platelet aggregation. Trans Assoc Am Phys 1986; 99: 0226-0235
3 De Marco L, Girolami A, Zimmermann TS, Ruggeri Z. von Willebrand factor interaction with the glycoprotein IIb/IIIa complex; its role in platelet function as demonstrated in patients with congenital afibrinogenemia. J Clin Invest 1986; 77: 1272-1277
4 Xia Z, Frojmovic MM. Aggregation efficiency of activated normal or fixed platelets in a simple shear field: Effect of shear and fibrinogen occupancy. Biophys J 1994; 66: 2190-2201
5 Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I, Sakai K, Ruggeri Z. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest 1991; 87: 1234-1240
6 Berliner S, Niiya K, Roberts JR, Houghton RA, Ruggeri Z. Generation and characterization of peptide-specific antibodies that inhibit von Willebrand factor binding to glycoprotein IIb-IIIa without interacting with other adhesive molecules. Selectivity is conferred by Pro 1743 and other amino acid residues adjacent to the sequence Arg 1744-Gly 1745-Asp 1746. J Biol Chem 1988; 263: 7500-7505
7 Coller BS, Peerschke El, Scudder LE, Sullivan CA. Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor. Blood 1983; 61: 0099-0110
8 Coller BS, Peerschke El, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983; 72: 0325-0338
9 Girma J-P, Fressinaud E, Christophe O, Roualt C, Obert B, Takahashi Y, Meyer D. Aurin tricarboxylic acid inhibits platelet adhesion to collagen by binding to the 509-695 disulphide loop of von Willebrand factor and competing with glycoprotein Ib. Thromb Haemost 1992; 68: 0707-0713
10 Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Heliums JD. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 1986; 78: 1456-1461
11 Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Heliums JD. Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate and is resistant to aspirin. Blood 1988; 71: 1366-1374
12 Ikeda Y, Handa M, Kamata T, Kawano K, Kawai Y, Watanabe K, Kawakami K, Sakai K, Fukuyama M, Itagaki I. et al. Transmembrane calcium influx associated with von Willebrand factor binding to GPIb in the initiation of shear-induced platelet aggregation. Thromb Haemost 1993; 69: 0496-0502
13 Schor K, Darius H, Matzky R, Ohlendort R. The antiplatelet and cardiovascular actions of a new carbacyclic derivative (ZK 36374) – equipotent to PGI₂in vitro. Arch Pharm 1981; 316: 0252-0255
14 Goto S, Salomon DR, Ikeda Y, Ruggeri ZM. Characterization of the unique mechanism mediating the shear-dependent binding of soluble von Willebrand factor to platelets. J Biol Chem 1995; 270: 23352-23361
15 Weinstein M, Vosburgh E, Phillips M, Turner N, Chute-Rose L, Moake J. Isolation from commercial aurintricarboxylic acid of the most effective polymeric inhibitors of von Willebrand factor interaction with platelet glycoprotein Ib. Comparison with other polyanionic and polyaromatic polymers. Blood 1991; 78: 2291-2298
16 Shattil SJ, Budzynski A, Scrutton MC. Epinephrine induces platelet fibrinogen receptor expression, fibrinogen binding, and aggregation in whole blood in the absence of other excitatory agonists. Blood 1989; 73: 0150-0158
17 Shattil SJ, Cunningham M, Hoxie JA. Detection of activation platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. Blood 1987; 70: 0307-0315
18 Frojmovic MM, Wong T, van de Ven T. Dynamic measurements of the platelet membrane glycoprotein IIb-IIIa receptor for fibrinogen by flow cytometry. I. Methodology, theory and results for two distinct activators. BiophysJ 1991; 59: 0815-0827
19 Marguerie GA, Plow EF, Edgington TS. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem 1979; 254: 5357-5363
20 Peerschke El, Zucker MB, Grant RA, Egan JJ, Johnson MM. Correlation between fibrinogen binding to human platelets and platelet aggregability. Blood 1980; 55: 0841-0847
21 Marguerie GA, Plow EF. Interaction of fibrinogen with the platelet receptor: Kinetics and effect of pH and temperature. Biochem 1981; 20: 1074-1080
22 Frojmovic MM, Mooney RM, Wong T. Dynamics of platelet glycoprotein IIb-IIIa receptor expression and fibrinogen binding. I. Quantal activation of platelet subpopulations varies with adenosine diphosphate concentration. Biophys J 1994; 67: 2060-2068
23 Bell DN, Spain S, Goldsmith HL. The ADP-induced aggregation of human platelets in flow through tubes: I. Measurement of the concentration and size of single platelets and aggregates. Biophys J 1989; 56: 0817-0828
24 Bell DN, Spain S, Goldsmith HL. The ADP-induced aggregation of human platelets in flow through tubes: II. Effect of shear rate, donor sex and ADP concentration. Biophys J 1989; 56: 0829-0843
25 Rochon YP, Frojmovic MM. Dynamics of human neutrophil aggregation evaluated by flow cytometry. J Leukocyte Biol 1991; 50: 0434-0443
26 Smoluchowski Mvon. Versuch einer mathematischen Theorie der Koagu-lationskinetik kolloider Losungen. Z Phys Chem 1917; 92: 0129-0168
27 Wong T, Pedvis L, Frojmovic MM. Platelet size affects both micro-and macro-aggregation: contribution of platelet number, volume fraction and cell surface. Thromb Haemost 1989; 62: 0733-0741
28 George JN, Onofre AR. Human platelet surface binding of endogenous secreted factor-VUI-von-Willebrand-factor and platelet factor 4. Blood 1982; 59: 0194-0197
29 Azzam K, Cissé-Thiam M, Drouet L. The antithrombotic effect of aurin tricarboxylic acid in the guinea pig is not soley due to the interaction with the von Willebrand factor-GPIb axis. Thromb Haemost 1996; 75: 0203-0210
30 Strony J, Phillips M, Brands D, Moake J, Adelman B. Aurin tricarboxylic acid in a canine model of coronary artery thrombosis. Circulation 1990; 81: 1106-1114
31 Parker RI, Gralnick HR. Identification of platelet glycoprotein IIb/IIIa as the major binding site for released platelet-von Willebrand factor. Blood 1986; 68: 0732-0736
32 Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiological flow rates: Distinction from and prerequisite for adhesion through integrins. Cell 1991; 65: 0859-0873
33 Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84: 0289-0297
34 Wagner CT, Kroll MH, Chow J, Heliums JD, Schafer Al. Epinephrine and shear stress synergistically induce platelet aggregation via a mechanism that partially bypasses vWF-GP-Ib interactions. Biorheology 1996; 33 (03) 0209-0229