Trypsin, Tryptase, and Thrombin Polarize Macrophages towards a Pro-Fibrotic M2a Phenotype.
Trypsin, Tryptase, and Thrombin Polarize Macrophages towards a Pro-Fibrotic M2a Phenotype.
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DOI：
10.1371/journal.pone.0138748
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gomer RH
中科院分区：
文献类型：
--
作者：
White MJ;Gomer RH
对于伤口愈合和纤维化病变的形成，循环单核细胞进入组织并分化成称为纤维细胞和促纤维化M2 a巨噬细胞的成纤维细胞样细胞，其与成纤维细胞一起形成瘢痕组织。单核细胞也可以分化成经典活化的M1巨噬细胞和交替活化的M2巨噬细胞。蛋白酶凝血酶（在血液凝固过程中被激活）和类胰蛋白酶（由激活的肥大细胞释放）可增强成纤维细胞增殖和纤维细胞分化，但它们对巨噬细胞的影响尚不清楚。在这里，我们报告说，凝血酶，类胰蛋白酶，和蛋白酶胰蛋白酶偏向人类巨噬细胞分化的促纤维化M2 a表型表达高水平的半乳糖凝集素-3从非极化的单核细胞，或从M1和M2巨噬细胞，这些影响似乎通过蛋白酶激活受体。这些结果表明，蛋白酶可以通过影响成纤维细胞、纤维细胞和巨噬细胞来启动瘢痕组织形成。
For both wound healing and the formation of a fibrotic lesion, circulating monocytes enter the tissue and differentiate into fibroblast-like cells called fibrocytes and pro-fibrotic M2a macrophages, which together with fibroblasts form scar tissue. Monocytes can also differentiate into classically activated M1 macrophages and alternatively activated M2 macrophages. The proteases thrombin, which is activated during blood clotting, and tryptase, which is released by activated mast cells, potentiate fibroblast proliferation and fibrocyte differentiation, but their effect on macrophages is unknown. Here we report that thrombin, tryptase, and the protease trypsin bias human macrophage differentiation towards a pro-fibrotic M2a phenotype expressing high levels of galectin-3 from unpolarized monocytes, or from M1 and M2 macrophages, and that these effects appear to operate through protease-activated receptors. These results suggest that proteases can initiate scar tissue formation by affecting fibroblasts, fibrocytes, and macrophages.