Extracellular signal-regulated kinase 1/2 is involved in the activation of NADPH oxidase induced by FMLP receptor but not by complement receptor 3 in rat neutrophils.
This experiment was performed to clarify the role of extracellular signal-regulated kinase, ERK1/2, in NADPH oxidase-dependent O2- production in rat peritoneal neutrophils. When neutrophils were exposed to N-formyl-methionyl-leucyl-phenylalanine (fMLP) to stimulate an N-formyl peptide receptor, not only the production of O2- but also the activation of ERK1/2 was observed. The translocation of an NADPH oxidase component, p47(phox), from cytosol to membrane also occurred in neutrophils stimulated with fMLP. U0126, an ERK1/2 kinase inhibitor, inhibited both the production of O2- and the translocation of p47(phox) elicited by fMLP. On the other hand, when complement receptor 3 of neutrophils was stimulated with opsonized zymosan (OZ), weaker activation of ERK1/2 than that by fMLP was observed. In this case, U0126 showed no inhibition against the production of O2- and slight inhibition against the translocation of p47(phox). Large inhibition against the OZ-induced production of O2- was only observed in neutrophils treated with GF109203X, a PKC inhibitor. The present study indicates that receptor dependence exists in the ERK1/2 signaling pathway leading to the activation of NADPH oxidase.
Waki
Kenji
K
Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Inanami
Osamu
O
Yamamori
Tohru
T
Kuwabara
Mikinori
M
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015151:Immunoblotting; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D013997:Time Factors
D002070:Butadienes; D004791:Enzyme Inhibitors; D016177:Macrophage-1 Antigen; D009570:Nitriles; D010455:Peptides; D010750:Phosphoproteins; D044042:Receptors, Formyl Peptide; C113580:U 0126; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen