Characteristics and mechanism of neutrophil-mediated cytostasis induced by tumor necrosis factor.
After being treated with rTNF, polymorphonuclear neutrophils (PMN) were highly suppressive to the growth of four different tumor target cells, Raji, K562, UCLA-SO-M14, and U937. Neutralizing TNF with specific antibodies before PMN were treated blocked induction of the anti-proliferative activity against Raji. However, after PMN were exposed to TNF the cytostatic activity could not be reversed by the antibody or by washing off TNF, indicating that the continuous presence of TNF was not required for expression of the anti-proliferative function. Addition of the hydrogen peroxide (HP) scavenger, catalase, at the beginning of the assay inhibited the cytostatic activity, suggesting that HP was involved in suppressing the tumor cell growth. In contrast, other reactive oxygen species inhibitors such as superoxide dismutase, sodium azide, L-methionine, or deferoxamine did not inhibit the cytostasis. HP alone at above 10 microM was cytostatic to Raji cells. The presence of TNF did not increase the sensitivity of Raji to HP. TNF activated PMN to produce HP but the amount of HP released in the culture supernatant was too low for direct cytostasis. PMN also became more adherent after TNF treatment. Therefore, the TNF-induced cytostasis may be mediated by local high concentrations of HP produced by PMN.
Shau
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Division of Surgical Oncology, UCLA Medical Center, Los Angeles, CA 90024.
D002374:Catalase / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000502:physiology; D007106:Immune Sera / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D010101:Oxygen Consumption; D013482:Superoxide Dismutase / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D006131:Growth Inhibitors; D007106:Immune Sera; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D013936:Thymidine