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
1  Departments of Pathology and Molecular Medicine
,
Dragoslava Kika Veljkovic
1  Departments of Pathology and Molecular Medicine
,
Nola Fuller
1  Departments of Pathology and Molecular Medicine
,
Yasuaki Motomura
2  Medicine, McMaster University, Hamilton, Ontario, Canada
,
Jean Marc Massé
3  Département d’Hématologie, INSERM U567, Institut Cochin, Paris, France
,
Elisabeth M. Cramer
3  Département d’Hématologie, INSERM U567, Institut Cochin, Paris, France
4  Faculté de Médecine Paris-Ile de France-Ouest, France
,
Catherine P. M. Hayward
1  Departments of Pathology and Molecular Medicine
2  Medicine, McMaster University, Hamilton, Ontario, Canada
› Author Affiliations
Grant support: Supported by grant 42450 from the Canadian Institutes of Health Research (C.P.M.H.). C.P.M.H is supported by a Career Investigator Award from the Heart and Stroke Foundation of Ontario, a Canada Research Chair in Molecular Hemostasis from the Government of Canada and a Premier's Research Excellence Award from the Government of Ontario. D.K.V. is the recipient of a Focus on Stroke Doctoral Research Award from the Heart and Stroke Foundation and Canadian Institutes of Health Research.
Further Information

Publication History

Received: 26 February 2005

Accepted after major revision: 29 May 2005

Publication Date:
07 December 2017 (online)

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.