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Effect of Eosinophil Adhesion on Intracellular Signaling in Cholinergic Nerve Cells

Department of Medicine, RCSI, Beaumont Hospital, Dublin, Ireland; Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom; and Department of Dermatology, School of Medicine, University of Utah, Salt Lake City, Utah

Address correspondence to: Richard W. Costello, Department of Medicine, RCSI, Beaumont Hospital, Dublin 9, Ireland. E-mail: rcostello{at}rcsi.ie

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)-B 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-B 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-B and AP-1 in nerve cells, indicating that eosinophil adhesion may control nerve growth and phenotype.

Abbreviations: activator protein-1, AP-1 • electrophoretic mobility shift analysis, EMSA • extracellular signal–regulated protein kinase, ERK • intercellular adhesion molecule-1, ICAM-1 • mitogen-activated protein kinase(s), MAP kinases • nuclear factor-B, NF-B • vascular cell adhesion molecule-1, VCAM-1 • very late antigen-4, VLA-4

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