Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor.
Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor.
复制标题
缺乏N-甲基肽受体的小鼠中抗菌宿主防御受损。
DOI：
10.1084/jem.189.4.657
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发表时间：
1999-02-15
影响因子：
15.3
通讯作者：
Murphy, P M
中科院分区：
文献类型：
--
作者：
Gao, J L;Lee, E J;Murphy, P M
N-甲酰肽源自细菌和线粒体蛋白，并与哺乳动物吞噬细胞上的特定受体结合。由于结合在体外诱导趋化性和吞噬细胞的激活，因此推测体内N-甲酰肽受体信号传导可能在抗菌宿主防御中很重要，尽管缺乏直接证据。在这里，我们在缺乏由靶向基因破坏产生的高亲和力 N-甲酰肽受体 (FPR) 的小鼠中测试了这一假设。 FPR−/− 小鼠发育正常，但与野生型同窝小鼠相比，其对单核细胞增生李斯特氏菌攻击的敏感性增加，通过死亡率增加来衡量。 FPR−/− 小鼠在感染后 2 天（这是在特定细胞免疫反应发生之前）脾脏和肝脏中的细菌负荷也增加，表明先天免疫存在缺陷。与此一致的是，在 FPR−/− 小鼠中，中性粒细胞对原型 N-甲酰肽 fMLF（甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸）的体外趋化性和体内外周血动员均不存在。这些结果表明 FPR 在体内抗菌宿主防御中发挥作用。
N-formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific receptors on mammalian phagocytes. Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N-formylpeptide receptor signaling in vivo may be important in antimicrobial host defense, although direct proof has been lacking. Here we test this hypothesis in mice lacking the high affinity N-formylpeptide receptor (FPR), created by targeted gene disruption. FPR−/− mice developed normally, but had increased susceptibility to challenge with Listeria monocytogenes, as measured by increased mortality compared with wild-type littermates. FPR−/− mice also had increased bacterial load in spleen and liver 2 d after infection, which is before development of a specific cellular immune response, suggesting a defect in innate immunity. Consistent with this, neutrophil chemotaxis in vitro and neutrophil mobilization into peripheral blood in vivo in response to the prototype N-formylpeptide fMLF (formyl-methionyl-leucyl-phenylalanine) were both absent in FPR−/− mice. These results indicate that FPR functions in antibacterial host defense in vivo.