RSS-Feed abonnieren
DOI: 10.1055/s-0038-1649652
Platelet Aggregation Induced by Plasma from Type IIB von Willebrand’s Disease Patients Is Associated with an Increase in Cytosolic Ca2+ Concentration
Publikationsverlauf
Received 29. Juni 1992
Accepted after revision 14. Mai 1993
Publikationsdatum:
05. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199304/lookinside/thumbnails/10-1055-s-0038-1649652-1.jpg)
Summary
The effect of type IIB von Willebrand’s factor (vWF) on platelet cytosolic Ca2+ ion concentration, measured by means of the probe fura 2, was investigated. Seven patients with type IIB von Willebrand disease (vWD) were studied. Addition of type IIB vWD plasma to platelet suspensions induced a cytosolic calcium increase accompanied by platelet aggregation. Both processes were completely abolished by addition of the calciumchelating agent EGTA, indomethacin, peptide RGDS, and monoclonal antibodies blocking the vWF binding site on GPIb-IX (LJIB1) or the cytoadhesive receptor on GPIIb-IIIa (LJCP8). The ADP-scavenger apyrase and the protein kinase C-inhibitor staurosporine partially inhibited the rate of the cytosolic calcium increase. No direct correlation between the extent of Ca2+ rise and the phenotypic expression of IIB vWD, such as the degree of spontaneous platelet aggregation or thrombocytopenia was apparent. It is suggested that aggregation and cytosolic Ca2+ increase in platelets exposed to plasma from type IIB vWD patients is mediated by a self-potentiating mechanism involving both GPIb and GPIIb-IIIa receptors as well as the thromboxane biosynthetic pathway.
-
References
- 1 Sadler JE. Von Willebrand factor. J Biol Chem 1991; 266: 22777-22780
- 2 Ruggeri ZM, Ware J. The structure and function of von Willebrand factor. Thromb Haemostas 1992; 67: 594-599
- 3 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composi-tion of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325
- 4 Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand’s disease. N Engl J Med 1980; 302: 11047-11051
- 5 Ruggeri ZM, Lombardi R, Gatti L, Bader R, Valsecchi C, Zimmerman TS. Type IIB von Willebrand’s disease. Differential clearance of endogenous versus transfused large multimer von Willebrand factor. Blood 1982; 60: 1453-1456
- 6 Gralnick HR, Williams SB, McKeown LP, Rick ME, Maisonneuve P, Jenneau C, Sultan Y. Von Willebrand’s disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor. J Clin Invest 1985; 76: 1522-1529
- 7 Casonato A, Fabris F, Girolami A. Platelet aggregation and pseudothrombocytopenia induced by 1-desamino-8-d-arginine vasopressin (DDAVP) in type IIB von Willebrand’s disease patient. Eur J Haematol 1990; 45: 36-42
- 8 Donner M, Holmberg L, Nilsson IM. Type IIB von Willebrand’s disease with probable autosomal recessive inheritance and presenting thrombocytopenia in infancy. Br J Haematol 1987; 66: 349-354
- 9 Saba HI, Saba SR, Dent J, Ruggeri ZM, Zimmerman TS. Type IIB Tampa: A variant of von Willebrand disease with chronic thrombocy-topenia circulating platelet aggregates and spontaneous platelet aggregation. Blood 1985; 66: 282-286
- 10 De Marco L, Girolami A, Zimmerman TS, Ruggeri ZM. Interaction of purified IIB von Willebrand factor with the platelet membrane glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb-IIIa complex and initiates aggregation. Proc Natl Acad Sci 1985; 82: 7424-7428
- 11 De Marco L, Mazzuccato M, Del BenMG, Budde U, Federici AB, Girolami A, Ruggeri ZM. Type IIB von Willebrand factor with normal sialic acid content induces platelet aggregation in the absence of ristocetin: role of platelet activation, fibrinogen and two distinct membrane receptors. J Clin Invest 1987; 80: 475-482
- 12 Sakariassen KS, Nievelstein PFEM, Coller BS, Sixma JJ. The role of platelet membrane glycoproteins Ib and IIb-IIIa in platelet adherence to human artery subendothelium. Br J Haematol 1986; 63: 681-691
- 13 De Marco L, Mazzuccato M, De Roia D, Casonato A, Federici AB, Girolami A, Ruggeri ZM. Distinct abnormalities in the interaction of purified type IIA and IIB von Willebrand factor with the two platelet binding sites, glycoprotien complex Ib-IX and IIb-IIIa. J Clin Invest 1990; 86: 785-792
- 14 Ware J, Dent JA, Azuma H, Sugimoto M, Kyrle PA, Yoshioka A, Ruggeri ZM. Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet GPIb-IX receptor. Proc Natl Acad Sci USA 1991; 88: 2946-2950
- 15 Cooney KA, Nichols WC, Bruck ME, Bahou WF, Shapiro AD, Bowie EJW, Gralnick HR, Ginsburg D. The molecular defect in type IIB von Willebrand disease. Identification of four potential missense mutations within the putative GPIb binding domain. J Clin Invest 1991; 87: 1227-1233
- 16 Ribba AS, Lavergne JM, Bahnak BR, Derlon A, Pietu G, Meyer D. Duplication of metionine within the glycoprotein Ib binding domain of von Willebrand factor detected by denaturing gradient gel elec-trophoresis in a patient with type IIB von Willebrand disease. Blood 1991; 78: 1738-1743
- 17 Randi AM, Jorieux S, Tuley EA, Mazurier C, Sadler JE. Recombi-nant von Willebrand factor Arg578-Gln. A type IIB von Willebrand disease mutation affects binding to glycoprotein Ib but not to collagen or heparin. J Biol Chem 1992; 267: 21187-21192
- 18 Casonato A, Sartori MT, De Marco L, Girolami A. 1-Desamino-8-D-Arginine Vasopressin (DDAVP) infusion in Type IIB von Willebrand’s Disease: shortening of bleeding time and induction of a variable pseudothrombocytopenia. Thromb Haemostas 1990; 64: 117-120
- 19 Casonato A, Fabris F, Vicariotto M, Girolami A. The evaluation of factor VIII antigen by means of a simple slide test. Am J Clin Pathol 1985; 84: 197-211
- 20 Ruzzene M, Donella-Deana A, Alexandre A, Francesconi MA, Deana R. The antioxidant butylated hydroxytoluene stimulates platelet protein kinase C and inhibits subsequent protein phosphorylation induced by thrombin. Biochim Biophys Acta 1991; 1094: 121-129
- 21 Pollock WK, Rink TJ, Irvine RV. Liberation of [3H]arachidonic acid and changes in cytosolic free calcium in fura-2-loaded platelets stimulated by ionomycin and collagen. Biochem J 1986; 253: 869-877
- 22 Handa M, Titani K, Holland LL, Roberts JR, Ruggeri ZM. The von Willebrand factor binding domain of platelet membrane glycoprotein Ib. Characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragment. J Biol Chem 1986; 261: 12579-12585
- 23 Niiya K, Hodson E, Bader R, Byers-Ward V, Koziol JA, Plow EF, Ruggeri ZM. Increased surface expression of the membrane glycoprotein GPIIb-IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation. Blood 1987; 70: 475-483
- 24 Casonato A, Sartori MT, Bertomoro T, Fede T, Vasoin F, Girolami A. Pregnancy-induced worsening of thrombocytopenia in a patient with type IIB von Willebrand’s disease. Blood Coagulation Fibrinolysis 1991; 2: 33-40
- 25 Miller JL, Kupinski JM, Castella A, Ruggeri ZM. Von Willebrand factor binds to platelets and induces platelet aggregation in platelet-type but not type IIB von Willebrand’s disease. J Clin Invest 1983; 72: 1532-1542
- 26 Plow EF, Pierschbacher MD, Ruoslahti E, Marguerie GA, Ginsberg MH. The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets. Proc Natl Acad Sci USA 1985; 82: 8057-8061
- 27 Siess W. Molecular mechanism of platelet activation. Physiol Rev 1989; 69: 123-141
- 28 Rink TJ, Sage SO. Calcium signalling in human platelets. Annu Rev Physiol 1990; 52: 431-449
- 29 Phillip DR, Charo IF, Scarborough RM. GPIIb-IIIa: The responsive integrin. Cell 1991; 65: 359-365
- 30 Gulino D, Boudignon C, Zhang L, Concord E, Rabiet M-J, Marguerie G. Ca2+ binding properties of the platelet glycoprotein IIb ligand domain. J Biol Chem 1992; 267: 1001-1007
- 31 Brass LF. Ca2+ transport across the platelet plasma membrane. Role of membrane glycoproteins IIb and IIIa. J Biol Chem 1985; 3260: 2231-2236
- 32 De Marco L, Girolami A, Zimmerman TS, Ruggeri ZM. 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
- 33 Chow TW, Hellums JD, Moake JL, Kroll MH. Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation. Blood 1992; 80: 113-120
- 34 Savage B, Ruggeri ZM. Selective recognition of adhesive sites in surface-bound fibrinogen by glycoprotein IIb-IIIa on nonactivated platelets. J Biol Chem 1991; 266: 11227-11233
- 35 Savage B, Shattil SJ, Ruggeri ZM. Modulation of platelet function through adhesion receptors. J Biol Chem 1992; 267: 11300-11306
- 36 Sinigaglia F, Bisio A, Torti M, Balduini CL, Bertolino G, Balduini C. Effect of GPIIb-IIIa complex ligands on calcium ion movement and cytoskeleton organization in activated platelets. Biochem Biophys Res Commun 1988; 154: 258-264
- 37 Kroll MH, Harris TS, Moake JL, Handin AI. Von Willebrand factor binding to platelet GPIb initiates signals for platelet activation. J Clin Invest 1991; 88: 1568-1573
- 38 Brass LF, Shattil SJ. Identification and function of the high affinity binding sites for Ca2+ on the surface of platelets. J Clin Invest 1984; 73: 626-633
- 39 Powling MJ, Hardisty RM. Glycoprotein IIb-IIIa complex and Ca2+ influx into stimulated platelets. Blood 1985; 66: 731-734
- 40 Yamaguchi A, Yamamoto N, Kitagawa H, Tanoue K, Yamazaki H. Ca2+ influx mediated through the GPIIb-IIIa complex during platelet activation. FEBS Lett 1987; 225: 228-232
- 41 Suldan Z, Brass LF. Role of the glycoprotein IIb-IIIa complex in plasma membrane Ca2+ transport: a comparison of results obtained with platelets and erythroleukemia cells. Blood 1991; 78: 2887-2893
- 42 Gralnick HR, Williams SB, Morisato DK. Effect of multimeric structure of the factor VIII/von Willebrand factor protein on binding to platelets. Blood 1981; 58: 387-397
- 43 Federici AB, Bader R, Pagani S, Colibretti AL, De Marco L, Mannucci PM. Binding of von Willebrand factor (vWF) to glycoproteins (GPIb) and IIb-IIIa complex: affinity is related to multimeric size. Br J Haematol 1987; 73: 93-99