Gender-related variations and interaction of human neutrophil cyclooxygenase and oxidative burst metabolites

Gender-related variations in human neutrophil membrane bound oxidative metabolism were evaluated employing the calcium ionophore A23187. These included the measurement of cyclooxygenase metabolites of arachidonate by specific RIA determination of thromboxane B2 (TxB2), prostaglandin E2 (PGE2), and 6-Keto PGF1 (6KPGF) as well as the initiation of the oxidative burst by the quantitative evaluation of superoxide (O-2) reduction of nitroblue tetrazolium (NBT). Neutrophils from women generated 30% less TxB2 and PGE2 than those obtained from men. In contrast, the neutrophils from women demonstrated relatively higher O-2 production with a cyclic pattern of both TxB2 and O-2 which correlated with their menstrual cycle. The elevated O-2 generation appeared to inversely correlate with TxB2 production. Further, introduction of an intracellular oxygen centered radical (OCR) scavenger, sodium benzoate, for the hydroxyl (.OH) radical was observed to affect cyclooxygenase metabolism in a dose-response manner. At higher concentrations of sodium benzoate, i.e., 10(-2) M, TxB2 production was inhibited; in contrast, 10(-3) M sodium benzoate enhanced neutrophil TxB2 generation which was particularly marked during times of increased oxidative burst activity, i.e. O-2 production. We conclude that the decreased production of cyclooxygenase metabolites observed in neutrophils from women in part derive from an increased oxidative burst activity. This suggests that a regulatory mechanism may exist between the neutrophil membrane bound oxidative system(s) involving oxygen centered radicals generated during both the oxidative burst and prostaglandin cyclic endoperoxide reduction. Further, these gender-related differences may be partially attributable to variations in circulating endogenous sex steroids.