title: Effect of eosinophil adhesion on intracellular signaling in cholinergic nerve cells.
abstract: Eosinophil localization to cholinergic nerves occurs in a variety of inflammatory conditions, including asthma. This localization is mediated by interactions between eosinophil integrins and neuronal vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Eosinophil-nerve cell interactions lead to generation of neuronal reactive oxygen species and release of eosinophil proteins. The effects of eosinophil adhesion on neuronal intracellular signaling pathways were investigated. Eosinophil adhesion to IMR32 cholinergic nerves led to a rapid and sustained activation of the nuclear transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1 in the nerve cells. Eosinophil binding to neuronal ICAM-1 led to a rapid activation of ERK1/2 in nerve cells. Inhibition of ERK1/2 prevented NF-kappaB activation. Eosinophil adhesion to VCAM-1 resulted in AP-1 activation, mediated partially by rapid activation of the p38 mitogen-activated protein kinase. These data show that adhesion of eosinophils induces mitogen-activated protein kinase-dependent activation of the transcription factors NF-kappaB and AP-1 in nerve cells, indicating that eosinophil adhesion may control nerve growth and phenotype.
authors.affiliation: Department of Medicine, RCSI, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Walsh
authors.forename: David R
authors.initials: DR
authors.lastname: Curran
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kingham
authors.forename: Ross K
authors.initials: RK
authors.lastname: Morgan
authors.forename: Niamh
authors.initials: N
authors.lastname: Durcan
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: W Graham
authors.initials: WG
authors.lastname: McLean
authors.forename: Richard W
authors.initials: RW
authors.lastname: Costello
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000109:Acetylcholine