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

Serezani CH, Aronoff DM, Sitrin RG, Peters-Golden M
Blood. 2009 114 (15): 3316-24

PMID: 19657115 · PMCID: PMC2759654 · DOI:10.1182/blood-2009-01-199919

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.

MeSH Terms (20)

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

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