FcγRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions
- 8 October 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 114 (15), 3316-3324
- https://doi.org/10.1182/blood-2009-01-199919
Abstract
Leukotriene (LT) B4 is generated in response to engagement of the Fcγ receptor (FcγR) and potently contributes to FcγR-mediated antimicrobial functions in pulmonary alveolar macrophages. In this study, we report that the LTB4 receptor leukotriene B4 receptor 1 (BLT1) redistributes from nonlipid raft (LR) to LR membrane microdomains upon immunoglobulin G–red blood cell, but not LTB4, challenge. Cholesterol depletion to disrupt LRs abolished LTB4-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 Gαi3, Src kinase, and FcγRI 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.Keywords
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