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Membrane type 1–matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium

AuthorsMatías-Román, Salomón; Gálvez, Beatriz G.; Genís, Laura; Yáñez-Mó, María; Rosa, Gonzalo de la; Sánchez-Mateos, Paloma; Sánchez-Madrid, Francisco; Arroyo, Alicia G.
KeywordsMembrane type 1–matrix metalloproteinase (MT1-MMP)
tumor-cell migration
Issue Date15-May-2005
PublisherAmerican Society of Hematology
CitationBlood, 105: 3956-3964 (2005)
AbstractMembrane type 1–matrix metalloproteinase (MT1-MMP) is involved in endothelial and tumor-cell migration, but its putative role in leukocyte migration has not been characterized yet. Here, we demonstrate that anti–MT1-MMP monoclonal antibody (mAb) impaired monocyte chemotactic protein-1 (MCP-1)–stimulated monocyte migration on fibronectin (FN), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). In addition, monocyte transmigration through tumor necrosis factor-α (TNF-α)–activated endothelium is also inhibited by anti–MT1-MMP mAb. Therefore, regulation of MT1-MMP in human peripheral blood monocytes was investigated. First, MT1-MMP clustering was observed at motility-associated membrane protrusions of MCP-1–stimulated monocytes migrating on FN, VCAM-1, or ICAM-1 and at the leading edge, together with profilin, of monocytes transmigrating through activated endothelial cells. In addition, up-regulation of MT1-MMP expression was induced in human monocytes upon attachment to FN in a manner dependent on α41 and α51 integrins. Binding of monocytes to TNF-α–activated human endothelial cells as well as to VCAM-1 or ICAM-1 also resulted in an increase of MT1-MMP expression. These findings correlated with an enhancement of MT1-MMP fibrinolytic activity in monocytes bound to FN, VCAM-1, or ICAM-1. Our data show that MT1-MMP is required during human monocyte migration and endothelial transmigration and that MT1-MMP localization, expression, and activity are regulated in monocytes upon contact with FN or endothelial ligands, pointing to a key role of MT1-MMP in monocyte recruitment during inflammation.
Description7 Figures
Publisher version (URL)http://bloodjournal.hematologylibrary.org/content/105/10/3956.full
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