Taurine chloramine inhibits PMA-stimulated superoxide production in human neutrophils perhaps by inhibiting phosphorylation and translocation of p47phox

Neutrophils produce microbicidal oxidants to destroy the invading pathogens using nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a membrane-associated enzyme complex that generates superoxide anion (O2−). Upon stimulation, the cytosolic components of NADPH oxidase, p47phox and p67phox and the small GTPase Rac move to phagosomal and plasma membranes where they become associated with the membrane components of NADPH oxidase, gp91phox and p22phox and express enzyme activity. We previously showed that taurine chloramine (Tau-Cl) inhibits O2− production in mouse peritoneal neutrophils (Kim, 1996). In the present study, we investigated the mechanisms underlying Tau-Cl-derived inhibition on O2− production using a human myeloid leukemia cell line, PLB-985 cell, which has been differentiated into neutrophil-like cell. Tau-Cl inhibited the phorbol myristate acetate (PMA)-elicited O2− production as previously observed in murine peritoneal neutrophils. Translocation of p47phox, p67phox and Rac was increased in response to PMA, and Tau-Cl inhibited the PMA-stimulated translocation of p47phox and p67phox to plasma membrane without affecting the translocation of Rac. In addition, Tau-Cl inhibited the PMA-derived phosphorylation of p47phox, a requirement for the translocation of cytosolic NADPH oxidase component to the plasma membrane. These results suggest that Tau-Cl inhibits PMA-elicited O2− production in PLB-985 granulocytes by inhibiting phosphorylation of p47phox and translocation of p47phox and p67phox, eventually blocking the assembly of NADPH oxidase complex.