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Thromb Haemost 2004; 92(03): 598-605
DOI: 10.1160/TH03-11-0689
Platelets and Blood Cells
Schattauer GmbH

Antibody cross-linking of human platelet P-selectin induces calcium entry by a mechanism dependent upon Fcγ receptor IIA

Jean G. Sathish   *
1   Department of Pharmacology, University of Bristol, UK
,
Shahrokh Falati
1   Department of Pharmacology, University of Bristol, UK
,
Kevin Croce
2   Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
,
Colin Crump   *
1   Department of Pharmacology, University of Bristol, UK
,
Barbara C. Furie
2   Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
,
Bruce Furie
2   Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
,
Alastair W. Poole
1   Department of Pharmacology, University of Bristol, UK
› Author AffiliationsFinancial support: This work was supported by grants to AWP from the BBSRC (UK), the British Heart Foundation (PG/2000087), the Wellcome Trust (064785 & 069572), and to BF & BCF from NIH (HL51926).
Further Information

Publication History

Received 13 November 2003

Accepted after revision 15 March 2004

Publication Date:
30 November 2017 (online)

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Summary

It is established that antibody-induced cross-linking of platelet surface receptors is able to activate platelets in a manner dependent upon FcγRIIA. This has not, however, previously been shown for the adhesion receptor P-selectin, and since there is evidence that P-selectin may couple to activation events, it was important to address whether antibody cross-linking of this receptor induced signalling events, and whether this was dependent on FcγRIIA. Here we show that although addition of soluble P-selectin ligand rPSGL-Ig alone is not able to induce calcium signalling, further addition of a full-length rabbit antihuman IgG leads to a sustained rise in [Ca2+]i.This was due to an increase in the frequency and amplitude of transient calcium spiking in single platelets. The response was dependent upon engagement of both P-selectin and FcγRIIA since blocking antibodies to either receptor inhibited the response. The calcium rise is mediated primarily by induction of a calcium entry mechanism involving the Na+-Ca2+ exchanger operating in reverse mode, since it was blocked by inhibitors of Na+-Ca2+ exchange, bepridil and 5 mM NiCl2.

Keywords

P-selectin - FcγRIIA - calcium - rPSGL-Ig - platelet

* Jean Sathish has subsequently moved to Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, UK. Colin Crump has moved to Department of Pathology, University of Cambridge, UK.


 

  • References

  • 1 Reilly MP, Taylor SM, Hartman NK. et al. Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcgammaRIIA. Blood 2001; 98: 2442-7.
    CrossrefPubMedGoogle Scholar
  • 2 Gratacap M-P, Herault J-P, Viala C. et al. FcγRIIA requires a Gi-dependent pathway for an efficient stimulation of phosphoinositide 3-kinase, calcium mobilisation, and platelet aggregation. Blood 2000; 96: 3439-46.
    PubMedGoogle Scholar
  • 3 Arnout J. The pathogenesis of the antiphospholipid syndrome: a hypothesis based on parallelisms with heparin-induced thrombocytopenia. Thromb Haemost 1996; 75: 536-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Hoylaerts MF, Thys C, Arnout J. et al. Recurrent arterial thrombosis linked to autoimmune antibodies enhancing von Willebrand factor binding to platelets and inducing Fc gamma RII receptor-mediated platelet activation. Blood 1998; 91 (08) 2810-7.
    PubMedGoogle Scholar
  • 5 Warkentin TE, Chong BH. Greinacher Heparin-induced thrombocytopenia: to-wards consensus. Thromb Haemost 1998; 79: 1-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Horne MK, Alkins BR. Platelet binding of IgG from patients with heparin-induced thrombocytopaenia. J Lab Clin Med 1996; 127: 435-42.
    CrossrefPubMedGoogle Scholar
  • 7 Turner CP, Hadley AG. The role of P-selectin in the immune destruction of platelets. Brit J Haematol 2003; 121: 623-31.
    CrossrefPubMedGoogle Scholar
  • 8 Horsewood P, Hayward CP, Warkentin TE. et al. Investigation of the mechanisms of monoclonal antibody-induced platelet activation. Blood 1991; 78: 1019-26.
    PubMedGoogle Scholar
  • 9 Anderson GP, Winkel JG, Anderson CL. Anti-GPIIb/IIIa (CD41) monoclonal antibodyinduced platelet activation requires Fc receptor-dependent cell-cell interaction. Brit J Haematol 1991; 79: 75-83.
    CrossrefPubMedGoogle Scholar
  • 10 Aiken ML, Ginsberg MH, Byers-Ward V. et al. Effects of OKM-5, a monoclonal antibody to glycoprotein IV, on platelet aggregation and thrombospondin surface expression. Blood 1990; 76: 2501-9.
    PubMedGoogle Scholar
  • 11 Worthington RE, Carroll RC, Boucheix C. Platelet activation by CD9 monoclonal antibodies is mediated by the FcgRII receptor. Brit J Haematol 1990; 74: 216-22.
    CrossrefPubMedGoogle Scholar
  • 12 Rubinstein E, Boucheix C, Worthington RE. et al. Anti-platlet antibody interactions with Fc gamma receptor. Semin Thromb Hemost 1995; 21 (01) 10-22.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Tomiyama Y, Kunicki TJ, Zipf TF. et al. Response of human platelets to activating monoclonal antibodies: importance of Fc gamma RII (CD32) phenotype and level of expression. Blood 1992; 80 (09) 2261-8.
    PubMedGoogle Scholar
  • 14 Sako D, Chang XJD, Barone KMD. et al. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell 1993; 75 (06) 1179-86.
    CrossrefPubMedGoogle Scholar
  • 15 Moore KL, Stults NL, Diaz S. et al. Identification of a specific glycoprotein ligand for P-selectin (CD62) on myeloid cells. J Cell Biol 1992; 118 (02) 445-56.
    CrossrefPubMedGoogle Scholar
  • 16 Norgard KE, Moore KL, Diaz S. et al. Characterization of a specific ligand for P-selection on myeloid cells. A minor glycoprotein with sialylated O-linked oligosaccharides. J Biol Chem 1993; 268 (17) 12764-74.
    PubMedGoogle Scholar
  • 17 Crockett-Torabi E. Selectins and mechanisms of signal transduction. J Leukoc Biol 1998; 63 (01) 1-14.
    CrossrefPubMedGoogle Scholar
  • 18 Crovello CS, Furie BC, Furie B. Rapid phosphorylation and selective dephosphorylation of P-selectin accompanies platelet activation. J Biol Chem 1993; 268 (20) 14590-3.
    PubMedGoogle Scholar
  • 19 Crovello CS, Furie BC, Furie B. Histidine phosphorylation of P-selectin upon stimulation of human platelets: a novel pathway for activation-dependent signal transduction. Cell 1995; 82 (02) 279-86.
    CrossrefPubMedGoogle Scholar
  • 20 Huang AJ, Manning JE, Bandak TM. et al. Endothelial cell cytosolic free calcium regulates neutrophil migration across monolayers of endothelial cells. J Cell Biol 1993; 120 (06) 1371-80.
    CrossrefPubMedGoogle Scholar
  • 21 Lorenzon P, Vecile E, Nardon E. et al. Endothelial cell E- and P-selectin and vascular cell adhesion molecule-1 function as signaling receptors. J Cell Biol 1998; 142 (05) 1381-91.
    CrossrefPubMedGoogle Scholar
  • 22 Dulkanchainun TS, Goss JA, Imagawa DK. et al. Reduction of hepatic ischemia/reperfusion injury by a soluble P-selectin glycoprotein ligand-1. Ann Surg 1998; 227: 832-40.
    CrossrefPubMedGoogle Scholar
  • 23 Kumar A, Villani MP, Patel UK. et al. Recombinant soluble form of PSGL-1 accelerates thrombolysis and prevents reocclusion in a porcine model. Circulation 1999; 99: 1363-9.
    CrossrefPubMedGoogle Scholar
  • 24 Scalia R, Hayward R, Armstead VE. et al. Effect of recombinant soluble P-selectin glycoprotein ligand-1 on leukocyte-endothelium interaction in vivo role in rat traumatic shock. Circ Res 1999; 84: 93-102.
    CrossrefPubMedGoogle Scholar
  • 25 Poole AW, Watson SP. Regulation of cytosolic calcium by collagen in single human platelets. Brit J Pharmacol 1995; 115: 101-6.
    CrossrefPubMedGoogle Scholar
  • 26 Ishida T, Matsuura H, Ishida-Kainouchi M. et al. Na(+)-Ca2+ exchange modulates Ca2+ handling of human platelets by altering intracellular Ca2+ store size. J Hypertens 1993; 11 (10) 1089-95.
    CrossrefPubMedGoogle Scholar
  • 27 Horackova M, Morash B, Byczko Z. Altered transarcolemmal Ca transport modifies the myofibrillar ultrastructure and protein metabolism in cultured adult ventricular cardiomyocytes. Mol Cell Biochem 2000; 204: 21-33.
    CrossrefPubMedGoogle Scholar
  • 28 Shiraga M, Tomiyama Y, Honda S. et al. Affinity modulation of the platelet integrin alpha IIb beta 3 by alpha- chymotrypsin: a possible role for Na+/Ca2+ exchanger. Blood 1996; 88: 2594-602.
    PubMedGoogle Scholar
  • 29 Shiraga M, Tomiyama Y, Honda S. et al. Involvement of Na+/Ca2+ exchanger in insideout signaling through the platelet integrin IIbbeta3. Blood 1998; 92 (10) 3710-20.
    PubMedGoogle Scholar
  • 30 Yanaga F, Poole A, Asselin J. et al. Syk interacts with tyrosine-phosphorylated proteins in human platelets activated by collagen and cross-linking of the Fcγ-IIA receptor. Biochem J 1995; 311 Pt (02) 471-8.
    CrossrefPubMedGoogle Scholar
  • 31 Gratacap MP, Payrastre B, Viala C. et al. Phosphatidylinositol 3,4,5-trisphosphate-dependent stimulation of phospholipase C-gamma2 is an early key event in FcgammaRIIA-mediated activation of human platelets. J Biol Chem 1998; 273: 24314-21.
    CrossrefPubMedGoogle Scholar
  • 32 Kinlough-Rathbone RL, Packham MA, Guccione MA. et al. Characteristics of thrombindegranulated human platelets: development of a method that does not use proteolytic enzymes for deaggregation. Thromb Haemost 1991; 65: 403-10.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Kuroda K, Ozaki Y, Qi R. et al. FcγRII receptor-mediated platelet activation induced by anti-CD9 monoclonal antibody opens Ca2+ channels which are distinct from those associated with Ca2+ store depletion. J Immunol 1995; 155: 4427-36.
    PubMedGoogle Scholar
  • 34 Hussain JF, Mahaut-Smith MP. Reversible and irreversible intracellular Ca2+ spiking in single isolated human platelets. J Physiol 1999; 514: 713-8.
    CrossrefPubMedGoogle Scholar
  • 35 Heemskerk JW, Willems GM, Rook MB. et al. Ragged spiking of free calcium in ADP-stimulated human platelets: regulation of puff-like calcium signals in vitro and ex vivo. J Physiol 2001; 535: 625-35.
    CrossrefPubMedGoogle Scholar
  • 36 Heemskerk JW, Feijge MAH, Henneman L. et al. The Ca2+-mobilizing potency of -thrombin and thrombin-receptor-activating peptide on human platelets. Concentration and time effects of thrombin-induced Ca2+ signaling. Eur J Biochem 1997; 249: 547-55.
    CrossrefPubMedGoogle Scholar
  • 37 Heemskerk JWM, Hoyland J, Mason WT. et al. Spiking in cytosolic calcium concentration in single fibrinogen-bound fura-2-loaded human platelets. Biochem J 1992; 283: 379-83.
    CrossrefPubMedGoogle Scholar
  • 38 Qi R, Ozaki Y, Asazuma N. et al. FcgammaRII tyrosine phosphorylation differs between FcgammaRII cross-linking and platelet-activating anti-platelet monoclonal antibodies. Biochim Biophys Acta 1999; 1451: 353-63.
    CrossrefPubMedGoogle Scholar
  • 39 Hato T, Sumida S, Yasukawa M. et al. Induction of Ca2+ influx and mobilisation by a monoclonal antibody to CD9 antigen. Blood 1990; 75: 1087-91.
    PubMedGoogle Scholar
  • 40 Favier R, Lecompte T, Morel MC. et al. Calcium rise in human platelet elicited by anti-CD9 and -CD41 murine monoclonal antibodies. Thromb Res 1989; 55: 591-9.
    CrossrefPubMedGoogle Scholar
  • 41 Davis W, Sage SO, Allen JM. Cytosolic calcium elevationin response to Fc receptor cross-linking in undifferentiated and differentiated U937 cells. Cell Calcium 1994; 16: 29-36.
    CrossrefPubMedGoogle Scholar
  • 42 Sargeant P, Sage SO. Calcium signalling in platelets and other nonexcitable cells. Pharmacol Ther 1994; 64 (03) 395-443.
    CrossrefPubMedGoogle Scholar
  • 43 Sage SO. The Wellcome Prize Lecture. Calcium entry mechanisms in human platelets. Exp Physiol 1997; 82 (05) 807-23.
    CrossrefPubMedGoogle Scholar
  • 44 Batlle DC, Godinich M, LaPointe MS. et al. Extracellular Na+ dependency of free cytosolic Ca2+ regulation in aortic vascular smooth muscle cells. Am J Physiol 1991; 261: C845-856.
    CrossrefPubMedGoogle Scholar
  • 45 Matsuda T, Takuma K, Baba A. Na(+)-Ca2+ exchanger: physiology and pharmacology. Jpn J Pharmacol 1997; 74 (01) 1-20.
    CrossrefPubMedGoogle Scholar
  • 46 Bose R, Li Y, Roberts DE. Na+/Ca2+ exchange in activated and non-activated human platelets. Ann N Y Acad Sci 2002; 976: 350-3.
    PubMedGoogle Scholar
  • 47 Roberts DE, Bose R. Reverse mode Na+/Ca2+ exchange in the collagen activation of human platelets. Ann N Y Acad Sci 2002; 976: 345-9.
    CrossrefPubMedGoogle Scholar
  • 48 Watanabe Y, Kimura J. Blocking effect of bepridil on Na+/Ca2+ exchange current in guinea pig cardiac ventricular myocytes. Jpn J Pharmacol 2001; 85 (04) 370-5.
    CrossrefPubMedGoogle Scholar