Activation-dependent surface expression of gC1qR/p33 on human blood platelets

Ellinor I. B. Peerschke; Tara K. Murphy; Berhane Ghebrehiwet

doi:10.1055/s-0037-1613450

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 89(02): 331-339
DOI: 10.1055/s-0037-1613450

Platelets and Blood Cells

Schattauer GmbH

Activation-dependent surface expression of gC1qR/p33 on human blood platelets

Ellinor I. B. Peerschke

¹Department of Pathology, Weill Medical College of Cornell University, New York

,

Tara K. Murphy

¹Department of Pathology, Weill Medical College of Cornell University, New York

,

Berhane Ghebrehiwet

²Department of Medicine, SUNY at Stony Brook, Stony Brook, New York, USA

› Author Affiliations

Abstract

Summary

GC1qR/p33 (gC1qR) is expressed by a variety of somatic and cultured cells, including blood platelets. It interacts with several cellular, viral, bacterial, and plasma proteins, suggesting a potential role in thrombosis, inflammation, and infection. Considerable controversy has surrounded the surface membrane localization of gC1qR, however, since its cDNA sequence does not predict a traditional membrane-anchoring domain, and bears a typical mitochondrial targeting sequence. The present study examined gC1qR expression on resting and activated human blood platelets using flow cytometry and confocal microscopy with two monoclonal antibodies, 74.5.2 and 60.11, directed against gC1qR C-terminal amino acids 204-218, and N-terminal amino acids 76-93, respectively. Unstimulated platelets reacted minimally with either antibody. In contrast, platelet activation with TRAP, epinephrine, or ADP produced markedly increased gC1qR expression as reflected by 74.5.2 binding but not 60.11 binding. Platelet activation was verified using PAC-1 and anti CD 62 antibodies. Whereas PAC-1 binding to activated platelets could be reversed following platelet incubation with PGE₁, 74.5.2 binding remained unchanged, suggesting the sustained expression of gC1qR following platelet stimulation. The data further demonstrate that detection of cell surface gC1qR may be dependent on antibody specificity. The ability of gC1qR to bind proteins involved in complement, coagulation, and kinin systems, as well as viral and bacterial pathogens including S. aureus protein A, supports the hypothesis that gC1qR expressed on activated platelets may contribute directly to thrombosis, inflammation, and endovascular infections.

Keywords

gC1qR/p33 - platelets

Full Text

References

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