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

Carlos H. Serezani, David M. Aronoff, Robert G. Sitrin and Marc Peters-Golden

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.

  • Submitted January 20, 2009.
  • Accepted July 20, 2009.
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