HYDROGEN-PEROXIDE MODULATION OF THE SUPEROXIDE ANION PRODUCTION BY STIMULATED NEUTROPHILS

Hydrogen peroxide (H2O2) pretreatment of human neutrophils results in a suppression of the superoxide anion (O-2(-.)) production in response to surface-acting stimulants such as lipopolysaccharide (LPS) and ops onized zymosan. This effect was not observed when phorbol myristate ac etate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) or tumor nec rosis factor alpha (TNF alpha) were used as a stimuli. Since the respo nse to PMA and other stimuli was unimpaired by preincubation with H2O2 , we assume that the H2O2 modulated O-2(-.) production is probably due to alteration of the LPS receptor conformation rather than effecting directly NADPH-oxidase. The balance of rective oxygen species (ROS) pr oduced by neutrophils in the state of sepsis may thus be autoregulated by negative feedback phenomena of locally produced H2O2.