Sithu, Srinivas D., English, William R. ORCID: https://orcid.org/0000-0003-3024-2441, Olson, Paul, Krubasik, Davia, Baker, Andrew H., Murphy, Gillian and D'Souza, Stanley E.
(2007)
Membrane-type 1-matrix metalloproteinase regulates intracellular adhesion molecule-1 (ICAM-1)-mediated monocyte transmigration.
Journal of Biological Chemistry, 282 (34).
pp. 25010-25019.
ISSN 0021-9258
Abstract
We examined the mechanism regulating intercellular cell adhesion molecule-1 (ICAM-1)-dependent monocyte transendothelial migration. Monocyte migration through endothelial cells expressing ICAM-1 alone was comparable to that of tumor necrosis factor-α-treated cells. Transmigration was reduced in ICAM-1 lacking the cytoplasmic tail and in tyrosine to alanine substitutions at Tyr-485 and Tyr-474. Tissue inhibitors of matrix metalloproteinases (TIMPs) −2 and −3 blocked transmigration, whereas TIMP-1 was ineffective. This profile suggested a role for membrane-type matrix metalloproteinases (MT-MMPs) in transmigration. Inhibitory antibodies and small interference RNA directed against MT1-MMP blocked transmigration, whereas overexpression of MT1-MMP in endothelial cells or monocytes promoted transmigration. MT1-MMP mediated the ectodomain cleavage of ICAM-1 that was blocked by TIMP-2 and −3. Overexpression of MT1-MMP rescued function in ICAM-1Y485A, and to a lesser extent in the cytoplasmic tail-deleted ICAM-1. In a binding assay, wild-type ICAM-1 bound to purified MT1-MMP while ICAM-1 mutants bound poorly. MT1-MMP co-localized with ICAM-1 at distinct structures in endothelial cells. MT1-MMP localization with cells expressing ICAM-1 mutations was reduced and diffused. These results indicate that the cytoplasmic tail of ICAM-1 regulates leukocyte transmigration through MT1-MMP interaction.
Item Type: | Article |
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Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences |
UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
Depositing User: | LivePure Connector |
Date Deposited: | 15 Dec 2022 10:31 |
Last Modified: | 19 Oct 2023 03:30 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/90196 |
DOI: | 10.1074/jbc.M611273200 |
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