title: Taurine chloramine inhibits PMA-stimulated superoxide production in human neutrophils perhaps by inhibiting phosphorylation and translocation of p47(phox).
abstract: 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 (O(2)(-)). Upon stimulation, the cytosolic components of NADPH oxidase, p47(phox) and p67(phox) and the small GTPase Rac move to phagosomal and plasma membranes where they become associated with the membrane components of NADPH oxidase, gp91(phox) and p22(phox) and express enzyme activity. We previously showed that taurine chloramine (Tau-Cl) inhibits O(2)(-) production in mouse peritoneal neutrophils (Kim, 1996). In the present study, we investigated the mechanisms underlying Tau-Cl-derived inhibition on O(2)(-) 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 O(2)(-) production as previously observed in murine peritoneal neutrophils. Translocation of p47(phox), p67(phox) and Rac was increased in response to PMA, and Tau-Cl inhibited the PMA-stimulated translocation of p47(phox) and p67(phox) to plasma membrane without affecting the translocation of Rac. In addition, Tau-Cl inhibited the PMA-derived phosphorylation of p47(phox), a requirement for the translocation of cytosolic NADPH oxidase component to the plasma membrane. These results suggest that Tau-Cl inhibits PMA-elicited O(2)(-) production in PLB-985 granulocytes by inhibiting phosphorylation of p47(phox) and translocation of p47(phox) and p67(phox), eventually blocking the assembly of NADPH oxidase complex.
authors.affiliation: Laboratory of Leukocyte Signaling Research and Center for Advanced Medical Education by BK21 Project, Inha University College of Medicine, Incheon 400-712, South Korea.
authors.forename: Hyung Sim
authors.initials: HS
authors.lastname: Choi
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Cha
authors.forename: Chaekyun
authors.initials: C
authors.lastname: Kim
mesh_terms: D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D013481:Superoxides; D013654:Taurine; C043410:N-chlorotaurine; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D013755:Tetradecanoylphorbol Acetate