Eosinophil migration induced by mast cell chymase is mediated by extracellular signal-regulated kinase pathway

Biochem Biophys Res Commun. 2005 Jul 15;332(4):969-75. doi: 10.1016/j.bbrc.2005.04.172.

Abstract

Mast cell chymase is known to induce eosinophil migration in vivo and in vitro. In the present study, we investigated possible involvement of mitogen-activated protein (MAP) kinases; extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38, in the chymase-induced eosinophil migration. Human chymase induced a rapid phosphorylation of ERK1/2 and p38 in human eosinophilic leukemia EoL-1 cells, while no phosphorylation was detected in JNK. The chymase-induced phosphorylation of ERK and p38 was inhibited by pertussis toxin. Similar results were obtained in the experiments using mouse chymase and eosinophils. U0126 (the inhibitor for MAP/ERK kinase) suppressed chymase-induced migration of EoL-1 cells and mouse eosinophils. However, SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) showed little effect on the migration. It is suggested therefore that chymase activates ERK and p38 probably through G-protein-coupled receptor, and that ERK but not p38 cascade may have a crucial role in chymase-induced migration of eosinophils.

MeSH terms

  • Animals
  • Anthracenes / pharmacology
  • Blotting, Western
  • Butadienes / pharmacology
  • Butyric Acid / chemistry
  • Cell Line, Tumor
  • Cell Movement
  • Chemotaxis
  • Chymases
  • Enzyme Inhibitors / pharmacology
  • Eosinophils / cytology*
  • Eosinophils / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Imidazoles / pharmacology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mast Cells / enzymology*
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nitriles / pharmacology
  • Pertussis Toxin / pharmacology
  • Phosphorylation
  • Pyridines / pharmacology
  • Receptors, G-Protein-Coupled / metabolism
  • Serine Endopeptidases / chemistry*
  • Serine Endopeptidases / physiology
  • Signal Transduction
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anthracenes
  • Butadienes
  • Enzyme Inhibitors
  • Imidazoles
  • Nitriles
  • Pyridines
  • Receptors, G-Protein-Coupled
  • U 0126
  • Butyric Acid
  • pyrazolanthrone
  • Pertussis Toxin
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Serine Endopeptidases
  • Chymases
  • SB 203580