title: Membrane type 1-matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium.
abstract: Membrane 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-alpha (TNF-alpha)-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 alpha4beta1 and alpha5beta1 integrins. Binding of monocytes to TNF-alpha-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.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Salomón
authors.initials: S
authors.lastname: Matías-Román
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Gálvez
authors.forename: Laura
authors.initials: L
authors.lastname: Genís
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
authors.forename: Gonzalo
authors.initials: G
authors.lastname: de la Rosa
authors.forename: Paloma
authors.initials: P
authors.lastname: Sánchez-Mateos
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: Alicia G
authors.initials: AG
authors.lastname: Arroyo
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D011485:Protein Binding; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D005353:Fibronectins; D039041:Integrin alpha4beta1; D039081:Integrin alpha5beta1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases