1. ¹Institute of Biochemistry I, Faculty of Medicine, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany
2. ²Department of Virology, Technical University Dresden, Dresden 01307, Germany

Correspondence: B Brüne, Johann Wolfgang Goethe-University, Institute of Biochemistry I, Faculty of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Tel: +49 69 6301 7423; Fax: +49 69 6301 4203; E-mail: bruene@zbc.kgu.de

Received 13 July 2005; Revised 4 November 2005; Accepted 7 November 2005; Published online 9 December 2005.

Abstract

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 C (PKC) activation. EMSA analysis demonstrated an immediate activation of peroxisome proliferator-activated receptor- (PPAR) following supplementation of AC to macrophages. In macrophages carrying a dominant-negative PPAR mutant, recognition of AC no longer suppressed PKC 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 PPAR activation.