Macrophage migration and invasion is regulated by MMP10 expression

Murray, Megan, Birkland, Timothy, Howe, Jonathan, Rowan, Andrew D., Fidock, Mark, Parks, William and Gavrilovic, Jelena (2013) Macrophage migration and invasion is regulated by MMP10 expression. PLoS One, 8 (5). ISSN 1932-6203

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Abstract

This study was designed to identify metalloproteinase determinants of macrophage migration and led to the specific hypothesis that matrix metalloproteinase 10 (MMP10/stromelysin-2) facilitates macrophage migration. We first profiled expression of all MMPs in LPS-stimulated primary murine bone marrow-derived macrophages and Raw264.7 cells and found that MMP10 was stimulated early (3 h) and down-regulated later (24 h). Based on this pattern of expression, we speculated that MMP10 plays a role in macrophage responses, such as migration. Indeed, using time lapse microscopy, we found that RNAi silencing of MMP10 in primary macrophages resulted in markedly reduced migration, which was reversed with exogenous active MMP10 protein. Mmp10−/− bone marrow-derived macrophages displayed significantly reduced migration over a two-dimensional fibronectin matrix. Invasion of primary wild-type macrophages into Matrigel supplemented with fibronectin was also markedly impaired in Mmp10−/− cells. MMP10 expression in macrophages thus emerges as an important moderator of cell migration and invasion. These findings support the hypothesis that MMP10 promotes macrophage movement and may have implications in understanding the control of macrophages in several pathologies, including the abnormal wound healing response associated with pro-inflammatory conditions.

Item Type: Article
Additional Information: © 2013 Murray et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Depositing User: Pure Connector
Date Deposited: 08 Oct 2014 08:48
Last Modified: 06 May 2022 01:23
URI: https://ueaeprints.uea.ac.uk/id/eprint/50299
DOI: 10.1371/journal.pone.0063555

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