Höpken U E, Lu B, Gerard N P, Gerard C
Ina Sue Perlmutter Cystic Fibrosis Laboratory, Children's Hospital, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Nature. 1996 Sep 5;383(6595):86-9. doi: 10.1038/383086a0.
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. 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.
已知一类G蛋白偶联趋化因子受体可介导中性粒细胞和巨噬细胞的转运与激活。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以及补体过敏毒素。这些受体明显的冗余性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作用，我们破坏了一个编码单一趋化因子受体的基因。在此我们表明，与野生型同窝小鼠相比，缺乏趋化因子C5a受体的小鼠尽管中性粒细胞流入显著增加，但仍无法清除肺内注入的铜绿假单胞菌，并死于肺炎。这些用亚致死剂量铜绿假单胞菌接种的C5a受体缺陷小鼠会被继发性细菌菌株超级感染。我们得出结论，C5a受体具有非冗余功能，是肺部黏膜宿主防御所必需的。
