Recognition of apoptotic cells by macrophages activates the peroxisome proliferator-activated receptor-γ and attenuates the oxidative burst

It is appreciated that phagocytosis of apoptotic cells (AC) is an immunological relevant process that shapes the proversus anti-inflammatory macrophage phenotype. It was our intention to study the respiratory burst, a prototype marker of macrophage activation, under the impact of AC. Following incubation of RAW264.7 macrophages with AC, we noticed attenuated production of reactive oxygen species (ROS) in response to PMA treatment, and observed a correlation between attenuated ROS formation and suppression of protein kinase C alpha (PKC alpha) activation. EMSA analysis demonstrated an immediate activation of peroxisome proliferator-activated receptor-gamma (PPAR gamma) following supplementation of AC to macrophages. In macrophages carrying a dominant-negative PPAR gamma mutant, recognition of AC no longer suppressed PKC alpha activation, and the initial phase of ROS formation was largely restored. Interference with actin polymerization and transwell experiments suggest that recognition of AC by macrophages suffices to attenuate the early phase of ROS formation that is attributed to PPARc activation.