title: FcgammaRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions.
abstract: 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.
authors: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109-5642, USA.
authors: Carlos H
authors: CH
authors: Serezani
authors: David M
authors: DM
authors: Aronoff
authors: Robert G
authors: RG
authors: Sitrin
authors: Marc
authors: M
authors: Peters-Golden
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007152:Immunologic Capping; D007710:Klebsiella Infections / Q000235:genetics / Q000378:metabolism*; D007711:Klebsiella pneumoniae; D007975:Leukotriene B4 / Q000235:genetics / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C485701:Fcgr1 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D002784:Cholesterol; D019061:src-Family Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C417708:Gnai3 protein, mouse