Download PDF
Thromb Haemost 1996; 75(04): 655-660
DOI: 10.1055/s-0038-1650338
Original Article
Schattauer GmbH Stuttgart

Porcine von Willebrand Factor Binding to Human Platelet GPIb Induces Transmembrane Calcium Influx

Mario Mazzucato
The Servizio Immunotrasfusionale e Analisi Cliniche, I.R.C.C.S., C.R.O., Aviano, PN, Italy
,
Luigi De Marco
The Servizio Immunotrasfusionale e Analisi Cliniche, I.R.C.C.S., C.R.O., Aviano, PN, Italy
,
Paola Pradella
The Servizio Immunotrasfusionale e Analisi Cliniche, I.R.C.C.S., C.R.O., Aviano, PN, Italy
,
Adriana Masotti
The Servizio Immunotrasfusionale e Analisi Cliniche, I.R.C.C.S., C.R.O., Aviano, PN, Italy
,
Francesco I Pareti
1   A. Bianchi Bonomi Hemophilia and Thrombosis Center, I.R.C.C.S., Maggiore Hospital, University of Milano, Italy
› Author Affiliations
Further Information

Publication History

Received 15 May 1995

Accepted after resubmission 18 December 1995

Publication Date:
10 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Porcine von Willebrand factor (P-vWF) binds to human platelet glycoprotein (GP) lb and, upon stirring (1500 rpm/min) at 37° C, induces, in a dose-dependent manner, a transmembrane flux of Ca2+ ions and platelet aggregation with an increase in their intracellular concentration. The inhibition of P-vWF binding to GP lb, obtained with anti GP lb monoclonal antibody (LJ-Ib1), inhibits the increase of intracellular Ca2+ concentration ([Ca2+]i) and platelet aggregation. This effect is not observed with LJ-Ib10, an anti GP lb monoclonal antibody which does not inhibit the vWF binding to GP lb. An anti GP Ilb-IIIa monoclonal antibody (LJ-CP8) shown to inhibit the binding of both vWF and fibrinogen to the GP IIb-IIIa complex, had only a slight effect on the [Ca2+]i rise elicited by the addition of P-vWF. No inhibition was also observed with a different anti GP IIb-IIIa monoclonal antibody (LJ-P5), shown to block the binding of vWF and not that of fibrinogen to the GP IIb-IIIa complex. PGE1, apyrase and indomethacin show a minimal effect on [Ca2+]i rise, while EGTA completely blocks it. The GP lb occupancy by recombinant vWF fragment rvWF445-733 completely inhibits the increase of [Ca2+]i and large aggregates formation. Our results suggest that, in analogy to what is seen with human vWF under high shear stress, the binding of P-vWF to platelet GP lb, at low shear stress and through the formation of aggregates of an appropriate size, induces a transmembrane flux of Ca2+, independently from platelet cyclooxy-genase metabolism, perhaps through a receptor dependent calcium channel. The increase in [Ca2+]i may act as an intracellular message and cause the activation of the GP IIb-IIIa complex.

 

  • References

  • 1 Gringeri A, Santagostino E, Tradati F, Giangrande PFL, Mannucci PM. Adverse effect of treatment with porcine factor VIII. Thromb Haemost 1991; 65: 245-247
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Forbes CD, Prentice CRM. Aggregation of human platelets by purified porcine and bovine antihaemophilic factor. Nature: New Biology 1973; 241: 149
    CrossrefPubMedGoogle Scholar
  • 3 Altieri D, Capitanio AM, Mannucci PM. vWF contaminating porcine factor VIII concentrate (Hyate:C) cause platelet aggregation. Br J Haematol 1986; 63: 703-714
    CrossrefPubMedGoogle Scholar
  • 4 Pareti FI, Mazzucato M, Bottini E, Mannucci PM. Interaction of porcine von Willebrand factor with the platelet glycoproteins lb and IMIIa complex. Br J Haematol 1992; 82: 81-86
    CrossrefPubMedGoogle Scholar
  • 5 De Marco L, Girolami A, Russel S, Ruggeri ZM. Interaction of Asialo von Willebrand factor with glycoprotein lb induces fibrinogen binding to the glycoprotein IIb/IIIa complex and mediates platelet aggregation. J Clin Invest 1985; 75: 1198-1203
    CrossrefPubMedGoogle Scholar
  • 6 De Marco L, Girolami A, Zimmerman TS, Ruggeri ZM. Interaction of purified type 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
    CrossrefPubMedGoogle Scholar
  • 7 Kroll M, Schaffer AI. Biochemical mechanisms of platelet activation. Blood 1989; 74: 1181-1195
    PubMedGoogle Scholar
  • 8 Ikeda Y, Handa M, Kamata T, Kawano K, Kawai Y, Watanabe K, Kawa-kami K, Sakai K, Fukuyama M, Itagaki I, Yoshioka A, Ruggeri ZM. Transmembrane calcium influx associated with von Willebrand factor binding to GPIb in the initiation of shear-induced platelet aggregation. Thromb Haemost 1993; 69: 496-502
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Kazal LA, Amsel S, Miller OP, Tocantins LM. The preparation of some properties of fibrinogen precipitated from human plasma by glycine. Proceedings of the Society for Experimental Biology and Medicine 1963; 113: 989-996
    PubMedGoogle Scholar
  • 10 Martinez J, Holbum RR, Shapiro SS, Erslev AJ. Fibrinogen Philadelphia. A hereditary hypodysfibrinogenemia characterized by fibrinogen hypercatabolism. J Clin Invest 1974; 53: 600-611
    CrossrefPubMedGoogle Scholar
  • 11 Handa M, Titani K, Holland LZ, Roberts JL, Ruggeri ZM. The von Willebrand factor binding domain of platelet membrane glycoprotein lb. Characterisation by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments. J Biol Chem 1986; 261: 12579-12585
    PubMedGoogle Scholar
  • 12 Lombardo VT, Hodson E, Roberts JR, Kunicki TJ, Zimmerman TS, Ruggeri ZM. Independent modulation of von Willebrand factor and fibrinogen binding to the platelet membrane glycoprotein IIb/IIIa complex as demonstrated by monoclonal antibody. J Clin Invest 1985; 76: 1950-1958
    CrossrefPubMedGoogle Scholar
  • 13 De Marco L, Mazzucato M, Masotti A, Fenton JW, Ruggeri ZM. Function of glycoprotein Iba in platelet activation induced by a-thrombin. J Biol Chem 1991; 266: 23776-23783
    PubMedGoogle Scholar
  • 14 Ey PL, Prowse SJ, Jenkin CR. Isolation of pure IgGl, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-Sepharose. Immunoche-mistry 1978; 15: 429-436
    CrossrefPubMedGoogle Scholar
  • 15 Fujmura Y, Titani K, Holland LZ, Roberts JR, Elder JH, Ruggeri ZM, Zimmerman TS. von Willebrand factor: a reduced and alkylated 52/48 fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein Ib. J Biol Chem 1986; 261: 381-385
    CrossrefPubMedGoogle Scholar
  • 16 Mohri H, Fujmura Y, Shima M, Yoshioka A, Houghten RA, Ruggeri ZM, Zimmerman TS. Structure of the von Willebrand factor domain interacting with glycoprotein lb. J Biol Chem 1988; 263: 17901-17904
    PubMedGoogle Scholar
  • 17 Sugimoto M, Ricca G, Hrinda ME, Schreiber AB, Searfoss GH, Bottini E, Ruggeri ZM. Functional modulation of the isolated glycoprotein lb binding domain of von Willebrand factor expressed in Escherichia coli. Biochemistry 1991; 30: 5202-5209
    CrossrefPubMedGoogle Scholar
  • 18 Walsh PN, Mills DCB, White JG. Metabolism and function of human platelets washed by albumin density gradient separation. Br J Haematol 1977; 36: 281-298
    CrossrefPubMedGoogle Scholar
  • 19 Ruggeri ZM, De Marco L, Gatti L, Bader R, Montgomery RR. Platelet have more than one binding site for von Willebrand Factor. J Clin Invest 1983; 72: 1-12
    CrossrefPubMedGoogle Scholar
  • 20 Pollock WK, Rink TJ, Irvine RF. Liberation of [3H]arachidonic acid and changes in cytosolic free calcium in fura-2-loaded platelets stimulated by ionomycin and collagen. Biochem J 1986; 235: 869-877
    CrossrefPubMedGoogle Scholar
  • 21 Vidar MS, Holmsen H, Aarbakke G. The platelet-stimulating effect of adrenaline through a2-adrenergic receptors requires simultaneous activation by a true stimulatory platelet agonist. Thromb Haemost 1993; 70: 506-513
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Machin S, Preston E. Guidelines on platelet function testing. J Clin Pathol 1988; 41: 1322-1330
    CrossrefPubMedGoogle Scholar
  • 23 Francesconi MA, Deana R, Girolami A, Pontara E, Casonato A. Platelet aggregation induced by plasma from type IIB von Willebrand’s disease patients is associated with an increase in cytosolic Ca2+ concentration. Thromb Haemost 1993; 70: 697-701
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Chow TW, Helium JD, Moake JL, Kroll MH. Shear stress-induced vWF binding to platelet glycoprotein lb initiates calcium influx associated with aggregation. Blood 1992; 80 (01) 113-120
    CrossrefPubMedGoogle Scholar
  • 25 De Marco L, Mazzucato M, De Roia D, Casonato A, Federici AB, Girolami A, Ruggeri ZM. Distinct abnormalities in the interaction of purified Types IIA and IIIB von Willebrand factor with the two platelet binding sites, glycoprotein complexes Ib-IX and IIB-IIIa. J Clin Invest 1990; 86: 785-792
    CrossrefPubMedGoogle Scholar
  • 26 Bahnak BR, Lavergne JM, Ferreira V, Kerbinov NablasD, Meyer D. Comparison of the primary structure of the functional domains of human and porcine von Willebrand factor that mediate platelet adhesion. Biochem Bio-phys Res Commun 1992; 182: 561-568
    CrossrefPubMedGoogle Scholar
  • 27 Ruggeri ZM, Ware JL, Ginsburg D. von Willebrand Factor. In: Thrombosis and Hemorrhage Loscalzo T, Schafer AI. (eds). Boston, MA: Blackwell Scientific Publications; 1994: 305-329
  • 28 Feinstein MB, Egan JJ, Sha’afi RI, White J. The cytoplasmic concentration of free calcium in platelets is controlled by stimulators of cyclic AMP production (PGD2, PGE1? Forskolin). Biochem Biophys Res Comm 1983; 113: 598-604
    CrossrefPubMedGoogle Scholar
  • 29 Moake JL, Turner NA, Stathopoulos NA, Nolasco L, 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
    PubMedGoogle Scholar
  • 30 Kroll MH, Harris TS, Moake JL, Handin RI, Schafer AI. von Willebrand Factor binding to platelet GP lb initiates signals for platelet activation. J Clin Invest 1991; 88: 1568-1573
    CrossrefPubMedGoogle Scholar
  • 31 Doni MG, Cavallini L, Alexandre A. Ca2+ influx in platelets: activation by the thrombin and by the depletion of the stores. Biochem J 1994; 303: 599605
    PubMedGoogle Scholar
  • 32 Cavallini L, Alexandre A. Ca2+ efflux from platelets. Control by protein Kinase C and the filling state of the intracellular Ca2+ stores. Eur J Biochem 1994; 222: 693-702
    CrossrefPubMedGoogle Scholar
  • 33 Falcon C, Amout J, Vermylen J. Platelet aggregation in whole blood -Studies with a platelet counting technique - Methodological aspects and some applications. Thromb Haemost 1989; 61: 423-428
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Hause LL, Retzinger GS, Megan PA. A compartimental model of platelet aggregation in vitro: the kinetics of single platelets. Thromb Res 1989; 56: 133-146
    CrossrefPubMedGoogle Scholar
  • 35 Jackson SP, Schoenwaelder SM, Yuan Y, Rabinowitz I, Salem HH, Mitchell CA. Adhesion receptor activation of phosphatidylinositol 3-kinase. J Biol Chem 1994; 269 (43) 27093-27099
    PubMedGoogle Scholar
  • 36 Razdan K, Heliums JD, Kroll MH. Shear-stress-induced von Willebrand factor binding to platelets causes the activation of tyrosine kinases. Biochem J 1994; 302: 681-686
    CrossrefPubMedGoogle Scholar
  • 37 Andrews RK, Fox JEB. Identification of a region in the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX complex that binds to purified actin-binding protein. J Biol Chem 1992; 227 (26) 18605-18611
    PubMedGoogle Scholar
  • 38 Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science 1993; 260: 1124-1127
    CrossrefPubMedGoogle Scholar