Metalloproteases from Pseudomonas aeruginosa degrade human RANTES, MCP-1, and ENA-78
Metalloproteases from Pseudomonas aeruginosa degrade human RANTES, MCP-1, and ENA-78
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DOI：
10.1089/107999003766628151
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发表时间：
2003-06-01
影响因子：
2.3
通讯作者：
Denning, GM
中科院分区：
文献类型：
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作者：
Leidal, KG;Munson, KL;Denning, GM
革兰氏阴性细菌铜绿假单胞菌是一种机会性人类病原体，与医院获得性肺炎患者的急性肺部疾病和囊性纤维化患者的慢性进行性肺部疾病相关。这种细菌在自然环境中的一个独特特征是分泌各种各样的因子，以确保其生长和生存。然而，有证据表明，当存在于人类宿主中时，这些相同的因素可能导致疾病。在研究铜绿假单胞菌分泌因子对气道上皮细胞的影响过程中，我们观察到细菌条件培养基中的金属蛋白酶、纯化碱性蛋白酶和弹性蛋白酶、降解人RANTES、单核细胞趋化蛋白-1 （MCP-1）和上皮中性粒细胞活化蛋白-78 （ENA-78）。在相同条件下，白细胞介素-8 （IL-8）对蛋白水解的抗性明显增强。降解伴随着趋化活性的丧失。这些数据表明，铜绿假单胞菌的金属蛋白酶可以改变气道中关键免疫调节细胞因子的相对数量，因此，可能有助于在铜绿假单胞菌相关的肺部疾病中观察到的病理生理学。
The gram-negative bacterium Pseudomonas aeruginosa is an opportunistic human pathogen associated with both an acute lung disease in patients with hospital-acquired pneumonia and a chronic, progressive lung disease in individuals with cystic fibrosis. A unique characteristic of this bacterium in its natural environment is the secretion of a wide variety of factors designed to ensure its growth and survival. Evidence suggests, however, that when present in the human host, these same factors may contribute to disease. In the course of studying the effect of P. aeruginosa secretory factors on airway epithelial cells, we observed that metalloproteases in bacterial-conditioned medium, as well as purified alkaline protease and elastase, degraded human RANTES, monocyte chemotactic protein-1 (MCP-1), and epithelial neutrophil-activating protein-78 (ENA-78). Under identical conditions, interleukin-8 (IL-8) was significantly more resistant to proteolysis. Degradation was accompanied by a loss of chemotactic activity. These data suggest that metalloproteases from P. aeruginosa could alter the relative amounts of critical immunomodulatory cytokines in the airway and, thus, could contribute to the pathophysiology observed in P. aeruginosa-associated lung disease.