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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cholesterol / genetics
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Cholesterol / metabolism
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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Immunoglobulin G / genetics
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Immunoglobulin G / metabolism
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Immunologic Capping*
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Klebsiella Infections / genetics
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Klebsiella Infections / metabolism*
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Klebsiella pneumoniae*
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Leukotriene B4 / genetics
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Leukotriene B4 / metabolism
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Macrophages, Alveolar / metabolism*
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Membrane Microdomains / genetics
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Membrane Microdomains / metabolism*
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Mice
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Mice, Knockout
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Phagocytosis / genetics
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Phosphorylation / genetics
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Rats
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Rats, Wistar
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Receptors, IgG / genetics
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Receptors, IgG / metabolism*
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Receptors, Leukotriene B4 / genetics
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Receptors, Leukotriene B4 / metabolism*
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Signal Transduction / genetics
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src-Family Kinases / genetics
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src-Family Kinases / metabolism
Substances
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Fcgr1 protein, mouse
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Immunoglobulin G
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Receptors, IgG
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Receptors, Leukotriene B4
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Leukotriene B4
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Cholesterol
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src-Family Kinases
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GTP-Binding Protein alpha Subunits, Gi-Go
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Gnai3 protein, mouse