FcγRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions

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 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 Gαi3, Src kinase, and FcγRI within LRs. This association was dependent on Srcmediated 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. © 2009 by The American Society of Hematology.