Aberrant Oxygen Metabolism in Neoplastic Cells Injured by Cytotoxic Macrophages
The focus of this workshop is to explore the mechanisms by which leukocytes injure other cells. Macrophages are particularly unique cells to study for two reason. First, cytotoxicity may not always be manifested as a lytic event. The early work of Evans and Alexander clearly demonstrated the profound and long-term antimitotic effect macrophages exert on neoplastic targets (1). When death does occur it may be many hours following the arrest of cell division. In no other effector-target cell interaction is the complete cessation of reproduction so dissociable from cell death and such a paramount feature of cell injury. Secondly, the efficiency and spectrum of macrophage-mediated cytostasis is remarkable. Under appropriate in vitro conditions virtually all added cells of a given target cell line are prevented from dividing. Furthermore, of the numerous neoplastic cell types which have been studied, none are capable of dividing in the presence of macrophages which have differentiated to the cytotoxic state (2). Our contribution to this conference deals with macrophage cytostasis. We have studied metabolic changes which occur in neoplastic cells upon contact with mouse peritoneal cytotoxic macrophages (CM) in vitro. These studies followed an observation that macrophage-injured neoplastic cells developed an unusual carbohydrate dependence. It is possible that understanding changes which occur in target cells upon CM-induced injury may provide insight into defining the biochemical mechanisi (s) by which CM exert their universal antimitotic action.
KeywordsOxidative Phosphorylation Neoplastic Cell L1210 Cell Sodium Periodate Stationary Phase Cell
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