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

Blood. 2009 Oct 8;114(15):3316-24. doi: 10.1182/blood-2009-01-199919. Epub 2009 Aug 5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol / genetics
  • Cholesterol / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Immunoglobulin G / genetics
  • Immunoglobulin G / metabolism
  • Immunologic Capping*
  • Klebsiella Infections / genetics
  • Klebsiella Infections / metabolism*
  • Klebsiella pneumoniae*
  • Leukotriene B4 / genetics
  • Leukotriene B4 / metabolism
  • Macrophages, Alveolar / metabolism*
  • Membrane Microdomains / genetics
  • Membrane Microdomains / metabolism*
  • Mice
  • Mice, Knockout
  • Phagocytosis / genetics
  • Phosphorylation / genetics
  • Rats
  • Rats, Wistar
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism*
  • Receptors, Leukotriene B4 / genetics
  • Receptors, Leukotriene B4 / metabolism*
  • Signal Transduction / genetics
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism


  • Fcgr1 protein, mouse
  • Immunoglobulin G
  • Receptors, IgG
  • Receptors, Leukotriene B4
  • Leukotriene B4
  • Cholesterol
  • src-Family Kinases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Gnai3 protein, mouse