S100A10 regulates plasminogen-dependent macrophage invasion
S100A10 regulates plasminogen-dependent macrophage invasion
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DOI：
10.1182/blood-2010-01-264754
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发表时间：
2010-08-19
期刊：
影响因子：
20.3
通讯作者：
Waisman, David M.
中科院分区：
文献类型：
--
作者：
O'Connell, Paul A.;Surette, Alexi P.;Waisman, David M.
纤溶酶原激活系统在巨噬细胞响应炎症刺激的迁移中起着不可或缺的作用，纤溶酶原与其细胞表面受体的结合启动了这一过程。虽然我们实验室之前的研究已经表明纤溶酶原受体S100A10在癌细胞纤溶酶产生中的重要性，但该蛋白在巨噬细胞迁移中的潜在作用尚未被研究。使用巯基乙酸盐诱导腹膜炎症反应，我们首次证明，与野生型（WT）小鼠相比，在S100A10缺陷（S100A10(-/-)）小鼠中，巨噬细胞在24、48和72小时内穿过腹膜进入腹腔的迁移量减少了53%。此外，体内浸润Matrigel桥塞的s100a10缺陷巨噬细胞的数量比其WT对应细胞减少了8倍。与WT巨噬细胞相比，来自S100A10（-/-）小鼠的巨噬细胞在体外显示，通过基质屏障的纤溶蛋白依赖性入侵减少50%，纤溶蛋白生成减少45%。这种纤溶蛋白依赖性侵袭的丧失部分是由于s100a10缺陷巨噬细胞产生的纤溶蛋白减少和前mmp -9的激活减少。本研究确定了S100A10直接参与巨噬细胞对炎症刺激的招募。(血。2010;116 (7):1136 - 1146)
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 with 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 hours. Furthermore, the number of S100A10-deficient macrophages that infiltrated Matrigel plugs was reduced by 8-fold compared with their WT counterpart in vivo. Compared with 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 in part the result of 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. (Blood. 2010;116(7):1136-1146)