Stimulatory Effects of Peroxisome Proliferator-Activated Receptor- [Formula: see text] on Fc [Formula: see text] Receptor-Mediated Phagocytosis by Alveolar Macrophages

Alveolar macrophages abundantly express PPAR- [Formula: see text] , 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- [Formula: see text] agonists on the Fc [Formula: see text] receptor, which mediates phagocytosis of particles opsonized by binding of immunoglobulin G antibodies. We found that troglitazone, rosiglitazone, and 15-deoxy- [Formula: see text]-prostaglandin [Formula: see text] increase the ability of alveolar, but not peritoneal, macrophages to carry out phagocytosis mediated by the Fc [Formula: see text] receptor. 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- [Formula: see text] ligands stimulate phagocytosis of unopsonized materials, this is the first demonstration that they stimulate phagocytosis of opsonized materials as well.