8 other authors

The plasminogen activation system plays an integral role in the migration of macrophages in response to an inflammatory stimulus and the binding of plasminogen to its cell surface receptor initiates this process. Although previous studies from our laboratory have shown the importance of the plasminogen receptor, S100A10 in cancer cell plasmin production, the potential role of this protein in macrophage migration has not been investigated. Using thioglycollate to induce a peritoneal inflammatory response, we demonstrate for the first time that compared to wild-type (WT) mice, macrophage migration across the peritoneal membrane into the peritoneal cavity in S100A10-deficient (S100A10-/-) mice was decreased by up to 53 % at 24, 48 and 72 hr. Furthermore, the number of S100A10-deficient macrophages that infiltrated Matrigel plugs was reduced by 8-fold compared to their WT counterpart in vivo. Compared to WT macrophages, macrophages from S100A10-/- mice demonstrated a 50% reduction in plasmin-dependent invasion across a Matrigel barrier and a 45 % reduction in plasmin generation in vitro. This loss in plasmin-dependent invasion was due in part to a decreased generation of plasmin and a decreased activation of pro-MMP-9 by S100A10-deficient macrophages. This study establishes a direct involvement of S100A10 in macrophage recruitment in response to inflammatory stimuli