Phorbol myristate acetate enhances human polymorphonuclear neutrophil release of granular enzymes but inhibits chemokinesis.
The effects of the co-carcinogenic phorbol ester, phorbol myristate acetate (PMA), on N-formyl-Met-Leu-Phe (FMLP)-induced human polymorphonuclear leukocyte chemokinesis and release of granular lysozyme and beta-glucuronidase were compared with those of the inactive phorbol didecanoate (PDD). Release of the enzymes was enhanced by PMA but was unaffected by PDD which also had no effect on chemokinesis. In contrast, FMLP-induced chemokinesis was completely suppressed by PMA in a dose-dependent fashion (ID50 = 3.5 nM). PMA also inhibited the FMLP-induced increase in cytoplasmic calcium level, measured by the fluorescent indicator quin-2. These and other results suggest that although the diacylglycerol/protein kinase C system is involved in the positive regulation of certain neutrophil functions (degranulation and superoxide generation), if it is very powerfully stimulated, as with PMA, it has inhibitory actions on other neutrophil properties such as motility.
D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009113:Muramidase / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010703:Phorbol Esters / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010703:Phorbol Esters; D010704:Phorbols; C008876:phorbol-12,13-didecanoate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase; D005966:Glucuronidase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium