FcgammaRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions.
FcgammaRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions.
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DOI：
10.1182/blood-2009-01-199919
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发表时间：
2009-10
期刊：
影响因子：
20.3
通讯作者：
C. H. Serezani;D. Aronoff;R. G. Sitrin;M. Peters-Golden
中科院分区：
文献类型：
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作者：
C. H. Serezani;D. Aronoff;R. G. Sitrin;M. Peters-Golden
白三烯（LT）B（4）响应于Fc γ受体（Fc γ R）的结合而产生，并有效促进肺泡巨噬细胞中Fc γ R介导的抗菌功能。在这项研究中，我们报告了LTB（4）受体白三烯B（4）受体1（BLT 1）在免疫球蛋白G-红细胞（而不是LTB（4））激发后从非脂筏（LR）重新分布到LR膜微区。消耗胆固醇破坏LRs可消除LTB（4）诱导的吞噬作用、杀微生物活性和信号传导增强。BLT 1信号传导对LR完整性的依赖性与由BLT 1、其主要偶联的G蛋白G α 13、Src激酶和LR内的Fc γ RI组成的复合物的形成相关。这种关联依赖于Src介导的BLT 1磷酸化。这些数据确定了一种新的调节形式，其中巨噬细胞免疫受体的参与将刺激性G蛋白偶联受体招募到LR微结构域中，从而增强抗菌信号传导。
Leukotriene (LT) B(4) is generated in response to engagement of the Fc gamma receptor (Fc gamma R) and potently contributes to Fc gamma R-mediated antimicrobial functions in pulmonary alveolar macrophages. In this study, we report that the LTB(4) receptor leukotriene B(4) receptor 1 (BLT1) redistributes from nonlipid raft (LR) to LR membrane microdomains upon immunoglobulin G-red blood cell, but not LTB(4), challenge. Cholesterol depletion to disrupt LRs abolished LTB(4)-induced enhancement of phagocytosis, microbicidal activity, and signaling. The dependence on LR integrity for BLT1 signaling correlated with formation of a complex consisting of BLT1, its primary coupled G protein G alpha i3, Src kinase, and Fc gamma RI within LRs. This association was dependent on Src-mediated phosphorylation of BLT1. These data identify a novel form of regulation in which engagement of a macrophage immunoreceptor recruits a stimulatory G protein-coupled receptor into a LR microdomain with resultant enhanced antimicrobial signaling.