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Apoptosis and subsequent phagocytosis of apoptotic cells are important processes for normal tissue development, homeostasis and the resolution of inflammation. The cells are rapidly removed as intact bodies by cells in the surrounding tissue or by professional phagocytes. This highly regulated process prevents the release of intracellular debris reducing the likelihood of tissue damage and occurs as the fate of most dying cells during development and throughout the lifespan of an organism. Upon apoptosis induction phosphatidylserine (PS) is exposed in the outer leaflet of the plasma membrane and is recognized in a stereo-specific manner by the PS-specific phosphatidylserine receptor (Ptdsr). Based on the current knowledge this engagement seems to be crucial for engulfment to occur. Moreover, the binding of the Ptdsr on the apoptotic cells is not necessary for uptake of apoptotic cells; it is also thought to be important for the release of anti-inflammatory mediators (e.g. Tgf-beta, Il-10, PGE2)
In contrast to this hypothesis targeted inactivation of the mouse Ptdsr gene revealed some unexpected functions of Ptdsr during development. Ablation of Ptdsr activity causes perinatal lethality that is associated with multiple severe defects in tissue and organ differentiation (e.g. kidney, lung, intestine, eye) demonstration a fundamental role of Ptdsr during development. In addition, we observed no impairement of the clearance of apoptotic cells, neither in vivo during embryonic development nor in in vitro assays using fetal liver-derived macrophages. Our data suggest a novel essential role of Ptsdr during embryogenesis that is clearly distinct from apoptotic cell removal during tissue and organ differentiation.