Evidence that OH· production by human PMNs is related to prostaglandin metabolism

Abstract

Recent studies indicate that human granulocytes generate OH· during the phagocytosis of zymosan particles. Several theoretical considerations suggested to us that this OH· production might be related to prostaglandin metabolism, particularly the observation that OH· is generated by the reduction of hydroperoxides in microsomal systems. In our studies, we tested the importance of prostaglandin metabolism in the production of OH· by human granulocytes (PMNs). Indomethacin and aspirin at concentrations known to impair cyclooxygenase activity decreased OH· production by PMNs during the phagocytosis of zymosan particles. Phenol, which is known to alter prostaglandin metabolism, ablated OH· completely. None of these drugs at the concentrations used impaired the generation of O ^-₂ or H₂O₂ by PMNs, as indicated by their failure to diminish significantly the generation of chemiluminescence. Thus, the decrement in OH· production by these drugs could not be attributed to a nonspecific effect on the production of O ^-₂ or H₂O₂. These experiments therefore, indicate that the model for OH· production observed during prostaglandin synthesis with microsomal systems applies to human granulocytes.