Journal of Leukocyte Biology 49:352-359 (1991) © 1991 Wiley-Liss, Inc. Neutrophil Erythrotoxicity Induced by Phorbol Myristate Acetate: Mechanisms Involved in Neutrophil Activation

The capacity of phorbol myristate acetate (PMA) to prime neutrophil cytotoxic responses induced by a second stimulus was investigated. Treatment of neutrophils with low concentrations of PMA (0.2-0.5 ng/mI) for 18 hr at 37#{176}Cmarkedly enhanced cytotoxicity triggered by Ca2 ionophore A23l87, N-formyl-methionyl-Ieucyl-phenylalanine (FMLP) and PMA. Pretreatment with PMA also enabled neutrophils to mediate significant cytotoxicity when triggered by platelet-activating factor (PAF), a stimulus unable to induce untreated cells to display cytotoxicity. Conversely, neutrophil cytotoxicity trig-gered by immune complexes (IC) was not modified by PMA treatment, whereas cytolytic activity of neutrophils against antibody-sensitized target cells was significantly in-creased. Treatment with PMA concentrations higher than 1 ng/ml directly triggered neutrophil cytotoxicity. Interestingly, we found that PMA-triggered neutrophils were able to sustain maximal levels of cytotoxicity for at least 8 hr after stimulation. With regard to the mechanisms involved in neutrophil activation by PMA, we found that catalase but not superoxide dismutase (SOD) prevented neutrophil activation measured as 1) induction of cytotoxic responses, 2) increase of neutrophil adhesiveness to cell-free surfaces, and 3) inhibition of chemotactic responses to FMLP. These findings suggest that H202 may play a major role in neutrophil activation induced by PMA. Key words: PMA, cytotoxicity, hydrogen peroxid