Distinct roles for pneumolysin's cytotoxic and complement activities in the pathogenesis of pneumococcal pneumonia.
Distinct roles for pneumolysin's cytotoxic and complement activities in the pathogenesis of pneumococcal pneumonia.
复制标题
肺炎球菌溶血素的细胞毒性和补体活性在肺炎球菌肺炎发病机制中的独特作用。
DOI：
10.1164/ajrccm.153.4.8616564
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Janoff,EN
中科院分区：
文献类型：
--
作者：
Rubins,JB;Charboneau,D;Fasching,C;Berry,AM;Paton,JC;Alexander,JE;Andrew,PW;Mitchell,TJ;Janoff,EN
肺炎链球菌溶血素是肺炎链球菌的主要细胞毒素，通过促进肺内细菌生长和侵入血液而促进侵袭性肺炎球菌肺炎的早期发病。溶血素是一种多功能毒素，具有不同的溶细胞（“溶血”）和补体激活（“补体”）活性，已定位于分子的几个区域。为了表征肺炎球菌溶血素的溶血和补体特性对肺炎球菌肺炎发病机制的具体贡献，我们比较了2型S。pneumoniae突变株，其产生缺乏这些活性的肺炎球菌溶血素。肺炎球菌溶血素的溶血或补体活性的情况下，使突变株的毒性低于野生型菌株在肺部感染。溶血素的溶血活性与气管内滴注后3和6 h的急性肺损伤和细菌生长相关。相反，肺炎链球菌溶血素的补体活性与肺部感染后24小时的细菌生长和菌血症相关。溶血素的补体活性与肺泡毛细血管损伤程度或初始肺部感染时白细胞的募集无关。然而，肺炎球菌溶血素的补体活性抑制体外补体依赖性中性粒细胞杀伤试验中突变细菌的杀伤。因此，肺炎球菌溶血素的溶血和补体活性在感染的不同阶段和通过不同的机制对肺炎球菌肺炎的早期发病机制做出了特定的贡献。
Pneumolysin, the major Streptococcus pneumoniae cytotoxin, contributes to the early pathogenesis of invasive pneumococcal pneumonia by facilitating intrapulmonary bacterial growth and invasion into the blood. Pneumolysin is a multifunctional toxin, with distinct cytolytic ("hemolytic") and complement-activation ("complement") activities that have been mapped to several regions of the molecule. To characterize the specific contributions of pneumolysin's hemolytic and complement properties to the pathogenesis of pneumococcal pneumonia, we compared the in vivo effects of type 2 S. pneumoniae mutant strains, which produce pneumolysins deficient in these activities. The absence of either pneumolysin's hemolytic or complement activities rendered mutant strains less virulent than the wild-type strain during pulmonary infection. Pneumolysin's hemolytic activity correlated with acute lung injury and bacterial growth at 3 and 6 h after endotracheal instillation. In contrast, pneumolysin's complement activity correlated with bacterial growth and bacteremia at 24 h after pulmonary infection. Pneumolysin's complement activity was not associated with the degree of alveolar-capillary injury or recruitment of leukocytes during initial pulmonary infection. However, pneumolysin's complement activity inhibited killing of mutant bacteria in an in vitro complement-dependent neutrophil killing assay. Thus, both pneumolysin's hemolytic and complement activities made specific contributions to the early pathogenesis of pneumococcal pneumonia at different stages of infection and by different mechanisms.