Medicine, Dentistry & Health Sciences Collected Works - Research Publications

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Start date: 1993 × End date: 1999 × Author: Savill, John ×

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    CD36 GENE-TRANSFER CONFERS CAPACITY FOR PHAGOCYTOSIS OF CELLS UNDERGOING APOPTOSIS
    REN, Y ; SILVERSTEIN, RL ; ALLEN, J ; SAVILL, J (ROCKEFELLER UNIV PRESS, 1995-05-01)
    Phagocyte recognition and ingestion of intact cells undergoing apoptosis are key events in this generally important program of cell death. Insufficient phagocyte capacity for apoptotic cells can result in failure to clear dying cells before membrane integrity is lost, resulting in leakage of noxious cell contents and severe tissue damage. However, no means has been available to increase phagocytic clearance of apoptotic cells. We now report that transfection of the macrophage adhesion molecule CD36 into human Bowes melanoma cells specifically conferred greatly increased capacity to ingest apoptotic neutrophils, lymphocytes, and fibroblasts, comparable to that exhibited by macrophages. Furthermore, when CD36 was transfected into another cell type with limited capacity to take up apoptotic bodies, the monkey COS-7 cell, similar effects were observed. Therefore, CD36 gene transfer can confer "professional" capacity to ingest apoptotic cells upon "amateur" phagocytes.
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    THE SPECIFIC RECOGNITION BY MACROPHAGES OF CD8(+),CD45RO(+) T-CELLS UNDERGOING APOPTOSIS - A MECHANISM FOR T-CELL CLEARANCE DURING RESOLUTION OF VIRAL-INFECTIONS
    AKBAR, AN ; SAVILL, J ; GOMBERT, W ; BOFILL, M ; BORTHWICK, NJ ; WHITELAW, F ; GRUNDY, J ; JANOSSY, G ; SALMON, M (ROCKEFELLER UNIV PRESS, 1994-11-01)
    During viral infections, CD8+,CD45RO+ T populations expand. These primed cells express abundant levels of cytoplasmic granules that contain perforin and TIA-1. Recent work has suggested that the majority of this CD8+ population downregulates Bcl-2 protein expression and is destined to undergo apoptosis. In this study we have investigated the elimination of these apoptotic CD8+ T cells by both human monocyte-derived and murine bone marrow macrophages. We have found that these phagocytes recognize and ingest both apoptotic CD8+ and CD4+ T cells using an alpha v beta 3 (vitronectin receptor)/CD36/thrombospondin recognition system, with the same receptors being used in the recognition of apoptotic neutrophils. These data provide new evidence for a mechanism that enables the clearance of greatly increased populations of CD8+ effector cells which are found during viral infections. This enables cellular homeostasis to occur in the host upon resolution of viral diseases in vivo.