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

Free Radic Res. 2003 Jun;37(6):665-71. doi: 10.1080/1071576031000097517.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butadienes / pharmacology
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Immunoblotting
  • Macrophage-1 Antigen / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • NADPH Oxidases / metabolism*
  • Neutrophils / metabolism*
  • Nitriles / pharmacology
  • Oxygen / metabolism
  • Peptides / chemistry
  • Phosphoproteins / metabolism
  • Protein Transport
  • Rats
  • Receptors, Formyl Peptide / metabolism*
  • Time Factors

Substances

  • Butadienes
  • Enzyme Inhibitors
  • Macrophage-1 Antigen
  • Nitriles
  • Peptides
  • Phosphoproteins
  • Receptors, Formyl Peptide
  • U 0126
  • NADPH Oxidases
  • neutrophil cytosolic factor 1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Oxygen