N-formylpeptides induce two distinct concentration optima for mouse neutrophil chemotaxis by differential interaction with two N-formylpeptide receptor (FPR) subtypes. Molecular characterization of FPR2, a second mouse neutrophil FPR.
N-formylpeptides induce two distinct concentration optima for mouse neutrophil chemotaxis by differential interaction with two N-formylpeptide receptor (FPR) subtypes. Molecular characterization of FPR2, a second mouse neutrophil FPR.
复制标题
N-甲基肽通过与两种N-甲基肽受体（FPR）亚型的差异相互作用诱导小鼠中性粒细胞趋化性的两种不同浓度最佳。 FPR2的分子表征，第二小鼠中性粒细胞FPR。
DOI：
10.1084/jem.190.5.741
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发表时间：
1999-09-06
影响因子：
15.3
通讯作者：
Gao, J L
中科院分区：
文献类型：
--
作者：
Hartt, J K;Barish, G;Murphy, P M;Gao, J L
N-甲酰肽受体(FPR)是一种G蛋白偶联受体，介导哺乳动物吞噬细胞对细菌N-甲酰肽的趋化反应。在这里，我们展示了一个名为fpr-rs2的小鼠基因编码第二个对中性粒细胞有选择性的N-甲酰基肽受体亚型，我们暂时将其命名为FPR2。原型N-甲酰基肽FMLF在稳定表达FPR2的人胚胎肾(HEK)293细胞中诱导钙离子流动和趋化。∼5μM对钙离子通量和趋化作用的EC50比转染小鼠Fpr的HEK293细胞的相应值∼大100倍。与此一致的是，FMLF对正常小鼠中性粒细胞的趋化诱导了两个不同的浓度最适，但仅对FPR基因敲除小鼠的中性粒细胞诱导了高浓度的最适趋化。基于这些数据，我们假设高亲和力和低亲和力的N-甲酰基肽受体，分别是FPR2和FPR2，在体内可能作为中继器，通过N-甲酰基肽梯度的高和低浓度部分介导中性粒细胞的迁移。
The N-formylpeptide receptor (FPR) is a G protein–coupled receptor that mediates mammalian phagocyte chemotactic responses to bacterial N-formylpeptides. Here we show that a mouse gene named Fpr-rs2 encodes a second N-formylpeptide receptor subtype selective for neutrophils which we have provisionally named FPR2. The prototype N-formylpeptide fMLF induced calcium flux and chemotaxis in human embryonic kidney (HEK) 293 cells stably transfected with FPR2. The EC50s, ∼5 μM for calcium flux and chemotaxis, were ∼100-fold greater than the corresponding values for mouse FPR-transfected HEK 293 cells. Consistent with this, fMLF induced two distinct concentration optima for chemotaxis of normal mouse neutrophils, but only the high concentration optimum for chemotaxis of neutrophils from FPR knockout mice. Based on these data, we hypothesize that high- and low-affinity N-formylpeptide receptors, FPR and FPR2, respectively, may function in vivo as a relay mediating neutrophil migration through the high and low concentration portions of N-formylpeptide gradients.