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Macrophage Migration and Invasion Is Regulated by MMP10 Expression

Lookup NU author(s): Emeritus Professor Drew Rowan

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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.

Publication metadata

Author(s): Murray MY, Birkland TP, Howe JD, Rowan AD, Fidock M, Parks WC, Gavrilovic J

Publication type: Article

Publication status: Published

Journal: PLoS ONE

Year: 2013

Volume: 8

Issue: 5

Online publication date: 14/05/2013

Acceptance date: 03/04/2013

Date deposited: 20/11/2014

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pone.0063555

DOI: 10.1371/journal.pone.0063555

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