Neutrophil elastase mediates Pseudomonas aeruginosa
Neutrophil elastase mediates Pseudomonas aeruginosa
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DOI：
10.4049/jimmunol.181.7.4945
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发表时间：
2008-10-01
影响因子：
4.4
通讯作者：
Belaaouaj, Azzaq
中科院分区：
文献类型：
--
作者：
Hirche, Tim O.;Benabid, Rym;Belaaouaj, Azzaq
中性粒细胞弹性蛋白酶（neutrophil elastase， NE）是一种中性粒细胞特异性丝氨酸蛋白酶，是铜绿假单胞菌感染相关宿主组织炎症和损伤的主要原因，严重时可导致死亡。在此，我们首次提供了令人信服的证据，表明宿主宁愿使用NE来保护自己免受铜绿假单胞菌感染。在临床相关的肺炎模型中，NE的靶向缺乏增加了小鼠对铜绿假单胞菌的敏感性。我们发现中性粒细胞对铜绿假单胞菌的最大胞内杀伤需要NE。在研究NE介导的P. aeruginosa杀伤机制时，我们发现NE降解了主要的外膜蛋白F，这是一种具有重要功能的蛋白，包括孔蛋白活性、维持结构完整性和感知宿主免疫系统激活。与此一致的是，使用外膜蛋白F缺失的等基因突变体否定了NE在宿主防御铜绿假单胞菌感染中的作用。
According to the widely accepted view, neutrophil elastase (NE), a neutrophil-specific serine protease, is a major contributor to Pseudomonas aeruginosa infection-associated host tissue inflammation and damage, which in severe cases can lead to death. Herein, we provide for the first time compelling evidence that the host rather employs NE to protect itself against P. aeruginosa infection. Using a clinically relevant model of pneumonia, targeted deficiency in NE increased the susceptibility of mice to P. aeruginosa. We found that NE was required for maximal intracellular killing of P. aeruginosa by neutrophils. In investigating the mechanism of NE-mediated killing of P. aeruginosa, we found that NE degraded the major outer membrane protein F, a protein with important functions, including porin activity, maintenance of structural integrity, and sensing of host immune system activation. Consistent with this, the use of an isogenic mutant deficient in outer membrane protein F negated the role of NE in host defense against P. aeruginosa infection.