Blockade of the Fas/FasL system improves pneumococcal clearance from the lungs without preventing dissemination of bacteria to the spleen
Blockade of the Fas/FasL system improves pneumococcal clearance from the lungs without preventing dissemination of bacteria to the spleen
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DOI：
10.1086/427261
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发表时间：
2005-02-15
影响因子：
6.4
通讯作者：
Martin, TR
中科院分区：
文献类型：
--
作者：
Matute-Bello, G;Liles, WC;Martin, TR
背景Fas/FasL系统是促凋亡和促炎的。FasL被诱骗受体-3（DcR 3）（一种天然存在的诱骗受体）抑制。我们测定了DcR 3类似物（DcR 3-a）对肺炎球菌肺炎小鼠Fas/FasL系统的全身阻断作用。将肺炎链球菌（7.2 x 10（5）或1.9 x 10（7）cfu/mL）注入未治疗的C57 Bl/6小鼠、DcR 3-a治疗的C57 Bl/6小鼠或Fas缺陷型lpr小鼠的气管内，48 h后对小鼠进行研究。在滴注较低的细菌剂量后，DcR 3-a或lpr突变对Fas/FasL系统的破坏导致肺部细菌清除率的提高（平均值+/- SE，分别为4.6 +/- 2.1 x 10（6）和3.5 +/- 1.6 x 10（6）cfu/肺，而未处理的C57 Bl/6小鼠为21.9 +/- 9.3 x 10（6）cfu/肺; P <0.05）和支气管肺泡灌洗液中多形中性粒细胞百分比降低（与未治疗的C57 B1/ 6小鼠相比，分别为平均值+/- SE和19.3% +/-9.5%;）。这些变化与肺内促炎细胞因子肿瘤坏死因子-α和巨噬细胞炎性蛋白-2浓度降低以及肺泡壁凋亡细胞减少相关（20.2% +/-7.8%55.0%+/-12.2%P <0.05）。肺中DcR 3-alpha阻断Fas/FasL系统可提高肺炎球菌肺炎小鼠的细菌清除率
Background. The Fas/FasL system is both proapoptotic and proinflammatory. FasL is inhibited by decoy receptor-3 (DcR3), a naturally occurring decoy receptor. We determined the effects of systemic blockade of the Fas/FasL system by a DcR3 analog (DcR3-a) in mice with pneumococcal pneumonia.Methods. Streptococcus pneumoniae (7.2 x 10(5) or 1.9 x 10(7) cfu/mL) was instilled intratracheally into untreated C57Bl/6 mice, C57Bl/6 mice treated with DcR3-a, or Fas-deficient lpr mice, and the mice were studied 48 h later.Results. After instillation of the lower bacterial dose, disruption of the Fas/FasL system by either DcR3-a or the lpr mutation resulted in improved clearance of bacteria in the lungs (mean +/- SE, and 4.6 +/- 2.1 x 10(6) and 3.5 +/- 1.6 x 10(6) cfu/lung, respectively, vs. 21.9 +/- 9.3 x 10(6) cfu/lung in untreated C57Bl/6 mice; P < .05) and decreased percentage of polymorphonuclear neutrophils in bronchoalveolar lavage fluid (mean +/- SE, and 19.3% +/- 9.5%, respectively, vs. in untreated C57Bl/ 6 mice;). These changes were associated 20.2% +/- 7.8% 55.0% +/- 12.2% P < .05 with decreased lung concentrations of the proinflammatory cytokines tumor necrosis factor-alpha and macrophage inflammatory protein-2 and with a decrease in apoptotic cells in the alveolar walls.Conclusion. Blockade of the Fas/FasL system by DcR3-alpha in the lungs improves clearance of bacteria in mice with pneumococcal pneumonia.