Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G
Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G
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DOI：
10.1016/s1074-7613(00)80173-9
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发表时间：
2000-02-01
期刊：
影响因子：
32.4
通讯作者：
Roes, J
中科院分区：
文献类型：
--
作者：
Tkalcevic, J;Novelli, M;Roes, J
虽然活性氧中间体（ROI）在多形核粒细胞的杀微生物活性中的关键作用已经确立，但体内非氧化效应机制的功能仍不清楚。在这里，我们表明，缺乏中性粒细胞颗粒丝氨酸蛋白酶弹性蛋白酶和/或组织蛋白酶G的小鼠容易受到真菌感染，尽管正常的中性粒细胞的发展和招聘。蛋白酶缺乏而不是感兴趣区的缺乏会导致对内毒素脂多糖致死作用的抵抗力增强，尽管会产生正常水平的肿瘤坏死因子α。这些数据证明了中性粒细胞的非氧化效应机制在宿主免疫和免疫病理学中的关键作用，并确定了弹性蛋白酶和组织蛋白酶G作为TNF α下游内毒素休克级联反应的效应物。
While the critical role of reactive oxygen intermediates (ROI) in the microbicidal activity of polymorphonuclear granulocytes is well established, the function of the nonoxidative effector mechanisms in vivo remains unclear. Here we show that mice deficient in the neutrophil granule serine proteases elastase and/or cathepsin G are susceptible to fungal infections, despite normal neutrophil development and recruitment. The protease deficiencies but not the absence of ROI leads to enhanced resistance to the lethal effects of endotoxin LPS, although normal levels of TNF alpha are produced. The data demonstrate a critical role of the nonoxidative effector mechanisms of neutrophils in host immunity and immunopathology and identify elastase and cathepsin G as effecters in the endotoxic shock cascade downstream of TNF alpha.