The C5a chemoattractant receptor mediates mucosal defence to infection
The C5a chemoattractant receptor mediates mucosal defence to infection
复制标题
DOI：
10.1038/383086a0
复制
发表时间：
1996-09-05
期刊：
影响因子：
64.8
通讯作者：
Gerard, C
中科院分区：
文献类型：
--
作者：
Hopken, UE;Lu, B;Gerard, C
已知G蛋白偶联化学引诱物受体家族介导中性粒细胞和巨噬细胞的转运和活化。该家族包括趋化因子受体，如白细胞介素-8、细菌甲酰化肽、血小板活化因子、白三烯B4和补体过敏毒素（1-3）。这些受体的明显冗余表明它们在宿主防御中具有重要的潜在作用。为了分离特定分子的贡献，我们破坏了编码单个趋化因子受体的基因。在这里，我们表明，与野生型同窝小鼠相比，趋化因子C5 a受体缺陷的小鼠无法清除肺内灌注的铜绿假单胞菌，尽管中性粒细胞流入显著增加，并死于肺炎，用假单胞菌亚致死接种物攻击的这些C5 a受体缺陷小鼠被次级细菌菌株超感染。我们得出结论，C5 a受体具有非冗余功能，并且是肺中粘膜宿主防御所需的。
A FAMILY of G-protein-coupled chemoattractant receptors is known to mediate the transport and activation of neutrophils and macrophages. This family includes receptors for chemokines, such as interleukin-8, bacterial formylated peptides, platelet-activating factor, leukotriene B4, and the complement anaphylatoxins(1-3). The apparent redundancy of these receptors suggests that they have an important underlying role in host defence. To isolate the contribution of particular molecules, we disrupted a gene that encodes a single chemoattractant receptor, Here we show that mice deficient in the chemoattractant C5a receptor, in comparison to their wild-type littermates, were unable to clear intrapulmonary-instilled Pseudomonas aeruginosa, despite a marked increase in neutrophil influx, and succumbed to pneumonia, These C5a-receptor-deficient mice challenged with sublethal inocula of Pseudomonas become superinfected with secondary bacterial strains. We conclude that the C5a receptor has a non-redundant function, and is required for mucosal host defence in the lung.