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Frdric Adam, Shilun Zheng, Nilesh Joshi, David S. Kelton, Amin Sandhu, Youko Suehiro, Samira B. Jeimy, Aurelio V. Santos, Jean-Marc Mass, John G. Kelton, Elisabeth M. Cramer, Catherine P. M. Hayward
Analyses of cellular multimerin 1 receptors: in vitro evidence of binding mediated by IIb3 and v3
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 IIb3 and v3. Endothelial cell binding to MMRN1 was predominantly mediated by v3 and did not require the MMRN1 RGD site or cellular activation. Like many other v3 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 IIb3 and v3.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 94, 11/2005
Pages: 1004 - 1011