Red cell regulation of tumor necrosis factor-induced human neutrophil cytostatic activity.
Tumor necrosis factor (TNF) activates polymorphonuclear neutrophils (PMN) to suppress tumor cell proliferation. This cytostatic activity could be blocked by the addition of red blood cells (RBC) into the assay. TNF-induced PMN cytostatic activity was mediated by hydrogen peroxide (H2O2). RBC have two major pathways to detoxify H2O2, one by catalase and the other by the glutathione redox cycle. Therefore, the catalase inhibitor 3-amino-1,2,4-triazole (AT) and the glutathione inhibitor N-ethylmaleimide (NE) were used to assess the role of each anti-oxidant in protecting the tumor target cells. RBC, depleted of catalase by AT, no longer protected Raji tumor cells from PMN cytostatic activity. However, depletion of reduced glutathione by NE had no effect on RBC protection of tumor target cells. Thus, RBC can protect tumor cells from cytostatic activity mediated by TNF-activated PMN, and the protection is a function of catalase, but not glutathione.
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Division of Surgical Oncology, UCLA School of Medicine 90024-1782.
D000640:Amitrole / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000097:blood; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004912:Erythrocytes / Q000502:physiology*; D005033:Ethylmaleimide / Q000494:pharmacology; D016166:Free Radical Scavengers; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; D002374:Catalase; D005978:Glutathione; D005033:Ethylmaleimide; D000640:Amitrole