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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    • "Thus, the C-type lectin, Dectin-1 (Brown & Gordon 2005), was recently shown to act in concert with the TLR-2 to activate macrophages exposed to b-glucans from the yeast candida albicans (Gantner et al. 2003). A number of these receptors also recognize endogenous inflammatory ligands including the scavenger receptors SR-A and CD36, both of which have been described to mediate the phagocytosis of apoptotic cells leading to a downregulation of macrophage activation (Savill et al. 1990; Ren et al. 1995; Savill et al. 2003). Thus, many of the factors that drive inflammation also double up in bringing about its reso- lution. "
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    International Journal of Experimental Pathology 05/2007; 88(2):85-94. DOI:10.1111/j.1365-2613.2006.00507.x · 2.05 Impact Factor
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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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    ABSTRACT: The thymus contains many apoptotic cells that arise from the process of positive and negative selection. Both thymic macrophages and thymic nurse cells/nursing thymic epithelial cells (nursing TECs), non-professional phagocytes, recognize and ingest apoptotic cells without inflammation or tissue damage. Previously we reported that human scavenger receptor class B (SR-B1) is involved in recognition of apoptotic thymocytes by nursing TECs. In this study, we examined the expression and role of a phosphatidylserine receptor (PSR). This receptor is believed to participate in the clearance of apoptotic cells. PSR was strongly expressed in nursing TECs. Transforming growth factor-beta augmented the expression of PSR leading to enhanced binding of apoptotic cells to nursing TECs. In nursing TECs, suppressed expression of human SR-B1 with anti-PSR antibody decreased binding of apoptotic thymocytes to nursing TECs. Our results suggest that both PSR and SR-B1 are expressed in nursing TECs and these receptors appear to play a major role in the clearance of apoptotic cells from the thymus.
    Journal of Molecular Endocrinology 05/2004; 32(2):497-505. · 3.62 Impact Factor
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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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    ABSTRACT: Cell death by apoptosis is characterized by specific biochemical changes, including the exposure of multiple ligands, expected to tag the dying cell for prompt recognition by phagocytes. In non-pathological conditions, an efficient clearance is assured by the redundant interaction between apoptotic cell ligands and multiple receptor molecules present on the engulfing cell surface. This review concentrates on the molecular interactions operating in mammalian and non-mammalian systems for apoptotic cell recognition, as well as on the consequences of their signaling. Furthermore, some cellular models where the exposure of the phosphatidylserine (PS) phospholipid, a classical hallmark of the apoptotic phenotype, is not followed by cell death will be discussed.
    Anais da Academia Brasileira de Ciências 04/2004; 76(1):93-115. DOI:10.1590/S0001-37652004000100009 · 0.88 Impact Factor