Serine protease cathepsin G regulates adhesion-dependent neutrophil effector functions by modulating integrin clustering
Serine protease cathepsin G regulates adhesion-dependent neutrophil effector functions by modulating integrin clustering
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DOI：
10.1016/j.immuni.2005.03.015
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发表时间：
2005-06-01
期刊：
影响因子：
32.4
通讯作者：
Pham, CTN
中科院分区：
文献类型：
--
作者：
Raptis, SZ;Shapiro, SD;Pham, CTN
多形核白细胞（PMN）衍生丝氨酸蛋白酶在免疫复合物（IC）介导的炎症中起关键作用。然而，这些蛋白酶调节炎症反应的机制在很大程度上仍不清楚。在这里，我们发现ic激活的组织蛋白酶G和中性粒细胞弹性酶缺陷（CG/NE） PMNs正常粘附在ic包被的表面，但没有经历CD11b聚集，也不能启动细胞骨架重组和细胞扩散。因此，CG/ ne缺乏的PMNs在MIP-2分泌和活性氧中间体产生方面表现出严重缺陷。外源性添加CG，但不具有蛋白水解活性的CG，足以恢复这些缺陷。这些发现确定了CG在整合素依赖性PMN效应功能中的重要作用，该功能独立于整合素依赖性粘附的下游。
The polymorphonuclear leukocyte (PMN)-derived serine proteases play a key role in immune complex (IC)-mediated inflammation. However, the mechanisms by which these proteases regulate inflammatory response remain largely undefined. Here, we show that IC-activated cathepsin G- and neutrophil elastase-deficient (CG/NE) PMNs adhered normally to IC-coated surfaces but did not undergo CD11b clustering and failed to initiate cytoskeletal reorganization and cell spreading. As a result, CG/NE-deficient PMNs exhibited severe defects in MIP-2 secretion and reactive oxygen intermediates production. Exogenously added CG, but not proteolytically inactive CG, was sufficient to restore these defects. These findings identify an important role for CG in integrin-dependent PMN effector functions that are separate from and downstream of integrin-dependent adhesion.