Analyses of cellular multimerin 1 receptors: in vitro evidence of binding mediated by αΙΙbβ3 and αvβ3

Frédéric Adam; Shilun Zheng; Nilesh Joshi; David S. Kelton; Amin Sandhu; Youko Suehiro; Samira B. Jeimy; Aurelio V. Santos; Jean-Marc Massé; John G. Kelton; Elisabeth M. Cramer; Catherine P.M. Hayward

doi:10.1160/TH05-02-0140

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(05): 1004-1011
DOI: 10.1160/TH05-02-0140

Platelets and Blood Cells

Schattauer GmbH

Analyses of cellular multimerin 1 receptors: in vitro evidence of binding mediated by αΙΙbβ3 and αvβ3

Authors

Frédéric Adam

¹Departments of Pathology and Molecular Medicine
Shilun Zheng

¹Departments of Pathology and Molecular Medicine
Nilesh Joshi

¹Departments of Pathology and Molecular Medicine
David S. Kelton

¹Departments of Pathology and Molecular Medicine
Amin Sandhu

¹Departments of Pathology and Molecular Medicine
Youko Suehiro

¹Departments of Pathology and Molecular Medicine
Samira B. Jeimy

¹Departments of Pathology and Molecular Medicine
Aurelio V. Santos

¹Departments of Pathology and Molecular Medicine
Jean-Marc Massé

³Département d'Hématologie, INSERM U567, Institut Cochin, Paris, France
John G. Kelton

²Medicine, McMaster University, Hamilton, Ontario, Canada
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

Abstract

Summary

Multimerin 1 (MMRN1) is a large, soluble, polymeric, factor V binding protein and member of the EMILIN protein family.In vivo, MMRN1 is found in platelets, megakaryocytes, endothelium and extracellular matrix fibers, but not in plasma. To address the mechanism of MMRN1 binding to activated platelets and endothelial cells, we investigated the identity of the major MMRN1 receptors on these cells using wild-type and RGE-forms of recombinant MMRN1. Ligand capture, cell adhesion, ELISA and flow cytometry analyses of platelet-MMRN1 binding, indicated that MMRN1 binds to integrins αIIbβ3 and αvβ3. Endothelial cell binding to MMRN1 was predominantly mediated by αvβ3 and did not require the MMRN1 RGD site or cellular activation. Like many other αvβ3 ligands, MMRN1 had the ability to support adhesion of additional cell types, including stimulated neutrophils. Expression studies, using a cell line capable of endothelial-like MMRN1 processing, indicated that MMRN1 adhesion to cellular receptors enhanced its extracellular matrix fiber assembly. These studies implicate integrin-mediated binding in MMRN1 attachment to cells and indicate that MMRN1 is a ligand for αIIbβ3 and αvβ3.

Keywords

Multimerin 1 - cell adhesion - integrin - platelet - endothelial cell

Full Text

References

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