Endocytosis and storage of plasma factor V by human megakaryocytes

Youko Suehiro; Dragoslava Kika Veljkovic; Nola Fuller; Yasuaki Motomura; Jean Marc Massé; Elisabeth M. Cramer; Catherine P. M. Hayward

doi:10.1160/TH05-02-0141

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(03): 585-592
DOI: 10.1160/TH05-02-0141

Platelets and Blood Cells

Schattauer GmbH

Endocytosis and storage of plasma factor V by human megakaryocytes

Youko Suehiro

¹Departments of Pathology and Molecular Medicine

,

Dragoslava Kika Veljkovic

¹Departments of Pathology and Molecular Medicine

,

Nola Fuller

¹Departments of Pathology and Molecular Medicine

,

Yasuaki Motomura

²Medicine, McMaster University, Hamilton, Ontario, Canada

,

Jean Marc Massé

³Département d’Hématologie, INSERM U567, Institut Cochin, Paris, France

,

Elisabeth M. Cramer

³Département d’Hématologie, INSERM U567, Institut Cochin, Paris, France

⁴Faculté de Médecine Paris-Ile de France-Ouest, France

,

Catherine P. M. Hayward

¹Departments of Pathology and Molecular Medicine

²Medicine, McMaster University, Hamilton, Ontario, Canada

› Author Affiliations

Abstract

Summary

Factor V is an essential coagulation cofactor that circulates in plasma and platelet α-granules where it is stored complexed to multimerin 1 (MMRN1). To gain insights into the origin and processing of human platelet factor V, and factor V-MMRN1 complexes, we studied factor V in cultured megakaryocytes. Factor V mRNA was detected in all megakaryocyte cultures. However, like albumin, IgG and fibrinogen, factorV protein was detectable only in megakaryocytes cultured with exogenous protein. The amount of factor V associated with megakaryocytes was influenced by the exogenous factorV concentration. Similar to platelet factor V, megakaryocyte factor V was proteolyzed and complexed with megakaryocyte-synthesized MMRN1. With secretagogues, megakaryocytes released factorV, IgG, fibrinogen and MMRN1. Immunofluorescent and electron microscopy confirmed factorV uptake by endocytosis and its trafficking to megakaryocyte α-granules. These data provide direct evidence that human megakaryocytes process plasma-derived factor V into α-granules and generate factor V-MMRN1 complexes from endogenously and exogenously synthesized proteins.

Keywords

Factor VIII - factor V - platelet activation markers - endocytosis - megakaryocytes / thrombopoiesis

Full Text

References

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