FcgammaRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions
| Title | FcgammaRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Serezani, CH, Aronoff DM, Sitrin RG, Peters-Golden M |
| Journal | Blood |
| Volume | 114 |
| Pagination | 3316-24 |
| Date Published | Oct 8 |
| ISBN Number | 1528-0020 (Electronic)0006-4971 (Linking) |
| Accession Number | 19657115 |
| Keywords | *Immunologic Capping, *Klebsiella pneumoniae, Animals, Cholesterol/genetics/metabolism, GTP-Binding Protein alpha Subunits, Gi-Go/metabolism, Immunoglobulin G/genetics/metabolism, Klebsiella Infections/genetics/*metabolism, Leukotriene B4/genetics/metabolism, Macrophages, Alveolar/*metabolism, Membrane Microdomains/genetics/*metabolism, Mice, Mice, Knockout, Phagocytosis/genetics, Phosphorylation/genetics, Rats, Rats, Wistar, Receptors, IgG/genetics/*metabolism, Receptors, Leukotriene B4/genetics/*metabolism, Signal Transduction/genetics, src-Family Kinases/genetics/metabolism |
| 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. |
| URL | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19657115 |