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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.


 

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