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 Blood, 8 October 2009, Vol. 114, No. 15, pp. 3316-3324.
Prepublished online as a Blood First Edition Paper on August 5, 2009; DOI 10.1182/blood-2009-01-199919.

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PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS

Fc{gamma}RI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions

Carlos H. Serezani1, David M. Aronoff2, Robert G. Sitrin1, and Marc Peters-Golden1

Divisions of 1 Pulmonary and Critical Care Medicine and 2 Infectious Diseases, Department of Internal Medicine, University of Michigan Health System, Ann Arbor

Leukotriene (LT) B4 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 LTB4 receptor leukotriene B4 receptor 1 (BLT1) redistributes from nonlipid raft (LR) to LR membrane microdomains upon immunoglobulin G–red blood cell, but not LTB4, challenge. Cholesterol depletion to disrupt LRs abolished LTB4-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.


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