Effects of phorbol myristate acetate on the metabolism and ultrastructure of neutrophils in chronic granulomatous disease.
Previous investigations have demonstrated that phorbol myristate acetate (PMA), the active principle of croton oil, stimulates alterations in normal polymorphonuclear leukocytes (PMN) that resemble closely the changes that develop in the cells after phagocytosis of bacteria. The present study has compared the effects of PMA and heat-killed bacteria on the oxygen uptake, glucose oxidation, nitroblue tetrazolium (NBT) reduction, and ultrastructure of normal neutrophils and PMN from six patients with chronic granulomatous disease (CGD). PMA stimulated oxygen consumption, hexose monophosphate shunt activity, and NBT reduction in normal cells but failed to produce similar effects in CGD neutrophils. However, PMA did induce formation of cytoplasmic vacuoles in the CGD cells similar to those observed in normal neutrophils. The results indicate that PMA is a useful nonparticulate agent for distinguishing between normal and CGD neutrophils and for studying basic mechanisms of phagocytosis in normal and abnormal PMN.
D000438:Alcohols / Q000494:pharmacology; D003436:Croton Oil / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies; D008297:Male; D008854:Microscopy, Electron; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption; D010585:Phagocyte Bactericidal Dysfunction / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis; D013778:Tetrazolium Salts / Q000378:metabolism
D000438:Alcohols; D004224:Diterpenes; D005227:Fatty Acids; D013778:Tetrazolium Salts; D003436:Croton Oil; D005947:Glucose