Fine-tuning phagocytic clearance of apoptotic cells by phosphatidylserine oxidation.
Matsura-T; Kai-M; Yamada-K; Shvedova-AA; Kagan-VE
J Clin Biochem Nutr 2004 Jan; 34(1):11-24
Apoptosis and subsequent phagocytosis are two essential components of the surveillance process that is responsible for removing unwanted or damaged cells without inflammation. During phagocytosis, the exposure of phosphatidylserine (PS) on the cell surface is known to serve as a recognizable ligand (an "eat-me" signal) for macrophage receptors. A growing body of evidence suggests that reactive oxygen species (ROS) are generated during apoptosis triggered by a variety of stimuli and are involved in the initiation and execution of apoptosis. Recent studies have focused on a potential role of ROS and subsequent oxidative stress in signal transduction rather than being a trivial trigger of cell damage and apoptosis. A new concept has been proposed in which it is hypothesized that the selective oxidation of PS during execution of the (intrinsic) apoptotic program may serve as an important signal for the externalization of PS, which may then participate in fine-tuning of clearance of apoptotic cells by phagocytes. This hypothesis is discussed in the present review, along with, the molecular mechanisms underlying preferential PS oxidation and its association with redox catalysis by the cytochrome c released from mitochondria into the cytosol.
Phagocytes; Cell-function; Cell-damage; Surveillance-programs; Oxidative-processes;
Author Keywords: phosphatidylserine oxidation; phosphatidylserine externalization; hydrogen peroxide; cytochrome c; apoptosis; phagocytosis
Division of Medical Biochemistry, Departmentof Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yomago 683-8503, Japan
Journal of Clinical Biochemical and Nutrition