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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

Frédéric Adam
1   Departments of Pathology and Molecular Medicine
,
Shilun Zheng
1   Departments of Pathology and Molecular Medicine
,
Nilesh Joshi
1   Departments of Pathology and Molecular Medicine
,
David S. Kelton
1   Departments of Pathology and Molecular Medicine
,
Amin Sandhu
1   Departments of Pathology and Molecular Medicine
,
Youko Suehiro
1   Departments of Pathology and Molecular Medicine
,
Samira B. Jeimy
1   Departments of Pathology and Molecular Medicine
,
Aurelio V. Santos
1   Departments of Pathology and Molecular Medicine
,
Jean-Marc Massé
3   Département d'Hématologie, INSERM U567, Institut Cochin, Paris, France
,
John G. Kelton
2   Medicine, McMaster University, Hamilton, Ontario, Canada
,
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 Financial support: Supported by a grant from the Heart and Stroke Foundation of Ontario (T 5248, C.P.M.H). C.P.M.H is supported by a Career Investigator Award from the Heart and Stroke Foundation of Ontario and a Canada Research Chair in Molecular Hemostasis from the Government of Canada.
Further Information

Publication History

Received: 26 February 2005

Accepted after revision: 01 September 2005

Publication Date:
14 December 2017 (online)

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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
 

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