Stimulatory Effects of Peroxisome Proliferator-Activated Receptor-gamma on Fcgamma Receptor-Mediated Phagocytosis by Alveolar Macrophages.
Alveolar macrophages abundantly express PPAR-gamma, 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-gamma agonists on the Fcgamma receptor, which mediates phagocytosis of particles opsonized by binding of immunoglobulin G antibodies. We found that troglitazone, rosiglitazone, and 15-deoxy-Delta12,14-prostaglandin J2 increase the ability of alveolar, but not peritoneal, macrophages to carry out phagocytosis mediated by the Fcgamma 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-gamma ligands stimulate phagocytosis of unopsonized materials, this is the first demonstration that they stimulate phagocytosis of opsonized materials as well.
Aronoff
David M
DM
Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System, Ann Arbor 48109, MI, USA.
Serezani
Carlos H
CH
Carstens
Jennifer K
JK
Marshall
Teresa
T
Gangireddy
Srinivasa R
SR
Peters-Golden
Marc
M
Reddy
Raju C
RC