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CUTTING EDGE |
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Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, London, United Kingdom;
Department of Biochemistry and Molecular Biology, University College London, London, United Kingdom;
Molecular Haematology Unit, Institute of Child Health, University College London, London, United Kingdom; and
Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom
Phagocytosis of apoptotic cells by macrophages and dendritic cells is necessary for clearance of proinflammatory debris and for presentation of viral, tumor, and self Ags. While a number of receptors involved in the cognate recognition of apoptotic cells by phagocytes have been identified, the signaling events that result in internalization remain poorly understood. Here we demonstrate that clearance of apoptotic cells is accompanied by recruitment of the Wiskott-Aldrich syndrome (WAS) protein to the phagocytic cup and that it’s absence results in delayed phagocytosis both in vitro and in vivo. Therefore, we propose that WAS protein plays an important and nonredundant role in the safe removal of apoptotic cells and that deficiency contributes significantly to the immune dysregulation of WAS. The efficiency of apoptotic cell clearance may be a key determinant in the suppression of tissue inflammation and prevention of autoimmunity.
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Y. Leverrier, K. Okkenhaug, C. Sawyer, A. Bilancio, B. Vanhaesebroeck, and A. J. Ridley Class I Phosphoinositide 3-Kinase p110{beta} Is Required for Apoptotic Cell and Fc{gamma} Receptor-mediated Phagocytosis by Macrophages J. Biol. Chem., October 3, 2003; 278(40): 38437 - 38442. [Abstract] [Full Text] [PDF]
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G. O. C. Cory, R. Garg, R. Cramer, and A. J. Ridley Phosphorylation of Tyrosine 291 Enhances the Ability of WASp to Stimulate Actin Polymerization and Filopodium Formation J. Biol. Chem., November 15, 2002; 277(47): 45115 - 45121. [Abstract] [Full Text] [PDF]
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