Recognition of apoptotic cells by macrophages activates the peroxisome proliferator-activated receptor-gamma and attenuates the oxidative burst.
It is appreciated that phagocytosis of apoptotic cells (AC) is an immunological relevant process that shapes the pro- versus 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 Calpha (PKCalpha) activation. EMSA analysis demonstrated an immediate activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) following supplementation of AC to macrophages. In macrophages carrying a dominant-negative PPARgamma mutant, recognition of AC no longer suppressed PKCalpha 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 PPARgamma activation.
Johann
A M
AM
Institute of Biochemistry I, Faculty of Medicine, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
von Knethen
A
A
Lindemann
D
D
Brüne
B
B
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D004789:Enzyme Activation; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009154:Mutation; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis; D051571:Protein Kinase C-alpha / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000199:Actins; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate