REGULATION OF NEUTROPHIL RESPIRATORY BURST BY PROTEIN PHOSPHATASES

Activation of human neutrophils involves a series of biochemical events which have been linked to the phosphorylation of specific proteins. Okadaic acid is an inhibitor of protein phosphatases 1 and 2A, and inhibits dephosphorylation of proteins in numerous cells. When human neutrophils were incubated with Okadaic acid prior to the stimulation with fMet-Leu-Phe (fMLP), an enhancement of superoxide anion release was seen. This enhancement was a result of a prolonged initial phase of superoxide release with a delay in the termination of the burst. In contrast, superoxide release in response to phorbol myristate acetate was inhibited. Okadaic acid had no effect on fMLP induced degranulation. These results indicate that dephosphorylation events, which are inhibited by Okadaic acid, have a role in regulating the rate and extent of the human neutrophils respiratory burst.