Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor
Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor
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DOI：
10.4049/jimmunol.180.6.4032
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发表时间：
2008-03-15
影响因子：
4.4
通讯作者：
Takeda, Kiyoshi
中科院分区：
文献类型：
--
作者：
Nishimura, Junichi;Saiga, Hiroyuki;Takeda, Kiyoshi
分泌性白细胞蛋白酶抑制剂（SLPT）具有多种功能，包括抑制蛋白酶活性、微生物生长和炎症反应。在这项研究中，我们证明，小鼠SLPI是至关重要的参与先天性宿主防御肺分枝杆菌感染。在牛分枝杆菌卡介苗呼吸道感染的早期阶段，SLPI由支气管和肺泡上皮细胞以及肺泡巨噬细胞产生，并分泌到肺泡腔中。重组小鼠SLPI通过破坏分枝杆菌细胞壁结构，有效抑制卡介苗和结核分枝杆菌的体外生长。SLPI中的两个乳清酸性蛋白结构域中的每一个都足以抑制分枝杆菌生长。SLPI的乳清酸性蛋白结构域内的阳离子残基是破坏分枝杆菌细胞壁所必需的。缺乏SLPI的小鼠对M.结核因此，小鼠SLPI是呼吸道粘膜表面对分枝杆菌的先天宿主防御的重要组成部分。
Secretory leukocyte protease inhibitor (SLPT) has multiple functions, including inhibition of protease activity, microbial growth, and inflammatory responses. In this study, we demonstrate that mouse SLPI is critically involved in innate host defense against pulmonary mycobacterial infection. During the early phase of respiratory infection with Mycobacterium bovis bacillus Calmette-Guerin, SLPI was produced by bronchial and alveolar epithelial cells, as well as alveolar macrophages, and secreted into the alveolar space. Recombinant mouse SLPI effectively inhibited in vitro growth of bacillus Calmette-Guerin and Mycobacterium tuberculosis through disruption of the mycobacterial cell wall structure. Each of the two whey acidic protein domains in SLPI was sufficient for inhibiting mycobacterial growth. Cationic residues within the whey acidic protein domains of SLPI were essential for disruption of mycobacterial cell walls. Mice lacking SLPI were highly susceptible to pulmonary infection with M. tuberculosis. Thus, mouse SLPI is an essential component of innate host defense against mycobacteria at the respiratory mucosal surface.