Article

Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis.

Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Nature (Impact Factor: 42.35). 02/1990; 343(6254):170-3. DOI: 10.1038/343170a0
Source: PubMed

ABSTRACT Phagocyte recognition of cells that have undergone apoptosis (programmed cell death) is an event of broad biological significance. Characterized by endogenous endonuclease activation, which results in chromatin fragmentation and nuclear condensation, apoptosis leads to swift ingestion of intact but 'senescent' or 'unwanted' cells by phagocytes in processes as diverse as the physiological involution of organs, the remodelling of embryonic tissues, and metamorphosis. The cell-surface mechanisms by which macrophages recognize apoptotic cells as 'senescent-self' have remained obscure. Here we report that macrophage recognition of apoptotic cells (both neutrophils and lymphocytes) is mediated by the vitronectin receptor, a heterodimer belonging to the beta 3 or cytoadhesin family of the integrins. Previously, the functions of the vitronectin receptor were believed to be limited to cell anchorage, but our findings indicate that the receptor has a novel and direct role in self-senescent-self intercellular recognition leading to macrophage phagocytosis of cells undergoing apoptosis.

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    • "phages recognize apoptotic cells is mediated through recognition of excess PS on the plasma membrane (Fadok et al. 1992a,b, Savill et al. 1993). Exposure of PS on the surface of apoptotic cells is associated with macrophage phagocytosis of selected cell phenotypes (Savill et al. 1990, Fadok et al. 1992a, 1993). Loss of membrane phospholipid asymmetry and the presence of PS on the externally present surface are features of many different cell types that undergo apoptosis. "
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    • "The importance of apoptotic cell recognition and clearance by phagocytes to tissue homeostasis is corroborated by the vast redundancy of ligands and receptors involved. Since the identification of the macrophage vitronectin receptor (α v β 3 integrin) as the first receptor to recognize and engulf apoptotic cells (Savill et al. 1990), several in vitro studies have characterized the participating molecules, mainly by inhibitory studies of the phagocytic process. The apoptotic cell is capped by various ''eat-me'' signals , that are recognized simultaneous or alternatively by distinct receptor molecules displayed by phagocytes (Figure 1). "
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