Stimulatory Effects of Peroxisome Proliferator-Activated Receptor-γon FcγReceptor-Mediated Phagocytosis by Alveolar Macrophages

Abstract

Alveolar macrophages abundantly express PPAR-γ, with both natural and synthetic agonists maintaining the cell in a quiescent state hyporesponsive to antigen stimulation. Conversely, agonists upregulate expression and function of the cell-surface receptor CD36, which mediates phagocytosis of lipids, apoptotic neutrophils, and other unopsonized materials. These effects led us to investigate the actions of PPAR-γagonists on the Fcγreceptor, which mediates phagocytosis of particles opsonized by binding of immunoglobulin G antibodies. We found that troglitazone, rosiglitazone, and 15-deoxy-Δ12,14-prostaglandinJ2increase the ability of alveolar, but not peritoneal, macrophages to carry out phagocytosis mediated by the Fcγreceptor. Receptor expression was not altered but activation of the downstream signaling proteins Syk, ERK-1, and ERK-2 was observed. Although it was previously known that PPAR-γligands stimulate phagocytosis of unopsonized materials, this is the first demonstration that they stimulate phagocytosis of opsonized materials as well.