Phorbol myristate acetate induced neutrophil autotoxicity.
The viability of neutrophils in the condition under which they kill neoplastic cells was studied. In the presence of phorbol myristate acetate (PMA) the 51Cr-release by human neutrophils was markedly stimulated. The PMA-induced 51Cr-release by neutrophils correlated well with the number of nonviable neutrophils as determined by the uptake of trypan blue. Phorbol myristate acetate had no effect on the 51Cr-release by lymphocytes, LPC-1 myeloma cells, ovarian ascites tumor cells, or neutrophils from a patient with chronic granulomatous disease. This suggests that the effect of PMA is not due to its nonspecific toxic effect; instead, it is dependent on the reactive oxygen species produced by the normal neutrophils. Catalase, cytochrome C, histidine, and methionine inhibited the PMA-induced 51Cr-release by human neutrophils, whereas superoxide dismutase, myeloperoxidase inhibitors, and some hydroxyl radical scavengers or singlet oxygen quenchers had no effect. The clumping of neutrophils induced by PMA was also important in the PMA-induced 51Cr-release by human neutrophils.
D002449:Cell Aggregation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D009101:Multiple Myeloma; D009504:Neutrophils / Q000502:physiology*; D010051:Ovarian Neoplasms; D010100:Oxygen / Q000378:metabolism; D010704:Phorbols / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen