Source: Annual Congress 2003 - Molecular biology of chronic lung disease and lung cancer
Disease area: Airway diseases

Abstract

RATIONALE: Eosinophils selectively localize and adhere to airway cholinergic nerves in asthma. Adhesion is mediated by neural ICAM-1 and VCAM-1. In vitro, this results in activation of reactive oxygen species and the transcription factor NF-kB in the cholinergic nerve cell line, IMR32. We examined the effect of eosinophil adhesion on IMR32 cell apoptosis induced by serum deprivation or cytokines. METHODS: Eosinophils or eosinophil membrane preparations from healthy donors were incubated with IMR32 cells in the presence or absence of cytokines (IL-1b (10ng/ml), TNFa (10ng/ml), IFN-g (25ng/ml)) or serum depletion to induce apoptosis. Some cells were pre-treated with MAP kinase or ICAM-1 plus VCAM-1 inhibitors. Apoptosis was quantified by flow cytometry using an Annexin-V assay and by nuclear Hoechst staining. Expression of the antiapoptotic genes Bfl-1 and Bcl-xl was examined by RT-PCR. RESULTS: Incubation with eosinophils or with purified eosinophil membranes resulted in protection of the nerve cells from cytokine induced apoptosis as detected by % of Annexin-V+ cells (p=0.012) and by Hoechst staining for nuclear condensation. This protection was associated with upregulation of Bfl-1 and Bcl-xl expression. Pre-treatment of the cells with ICAM-1 and VCAM-1 inhibitors or with ERK inhibitor negated this effect. CONCLUSIONS: These results suggest that adhesion of eosinophils to cholinergic nerve cells confers resistance to apoptosis by the upregulation of anti-apoptotic genes via an adhesion and MAP kinase dependent pathway.

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R. K. Morgan, M. T. Walsh, D. R. Curran, N. Durcan, R. W. Costello (Dublin, Ireland). Eosinophil adhesion to cholinergic nerves protects the nerves from apoptosis via the upregulation of anti-apoptotic BCl-2 proteins. Eur Respir J 2003; 22: Suppl. 45, 1499

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