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Title: | Membrane type 1–matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium |
Authors: | Matías-Román, Salomón; Gálvez, Beatriz G.; Genís, Laura; Yáñez-Mó, María; Rosa, Gonzalo de la; Sánchez-Mateos, Paloma; Sánchez-Madrid, Francisco; Arroyo, Alicia G. |
Keywords: | Membrane type 1–matrix metalloproteinase (MT1-MMP) tumor-cell migration |
Issue Date: | 15-May-2005 |
Publisher: | American Society of Hematology |
Citation: | Blood, 105: 3956-3964 (2005) |
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-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. |
Description: | 7 Figures |
Publisher version (URL): | http://bloodjournal.hematologylibrary.org/content/105/10/3956.full |
URI: | 10261/40320 |
DOI: | 10.1182/blood-2004-06-2382 |
ISSN: | 0006-4971 |
E-ISSN: | 1528-0020 |
Appears in Collections: | (CIB) Artículos |
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