T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:109

Article

Trautmann, A ; Schmid-Grendelmeier, P ; Krüger, K ; Crameri, R ; Akdis, M ; Akkaya, A ; Bröcker, EB ; Blaser, K ; Akdis, CA

关键词: apoptosis;    asthma;    bronchial epithelial cell;    eosinophil;    Fas;    interferon-gamma;    T cell;    tumor necrosis factor;   

DOI  :  10.1067/mai.2002.121460

来源: Elsevier

【 摘 要 】

Background: Asthma is an inflammatory airway disease associated with an infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (ECs). Objective: Shedding of bronchial ECs is characterized by loss of the normal bronchial pseudostratified epithelium and the maintenance of a few basal cells on a thickened basement membrane. The aim of this study was to investigate whether, and by which mechanism, T cells and eosinophils can cause damage to airway ECs. Methods: Bronchial ECs, cultured and exposed to cytokines, eosinophil cationic protein, activated T cells, and eosinophils were studied for the expression of apoptosis receptors (now cytometry, immunoblotting, and RNA expression) and for the susceptibility for undergoing apoptosis. In addition, bronchial biopsy specimens from patients with asthma were evaluated for EC apoptosis. Results: We demonstrate herein that the respiratory epithelium is an essential target of the inflammatory attack by T cells and eosinophils. Bronchial ECs underwent cytokine-induced cell death with DNA fragmentation and morphologic characteristics of apoptosis mediated by activated T cells and eosinophils. T cell- and eosinophil-induced EC apoptosis was blocked by inhibition of IFN-gamma and TNF-alpha; the Fas ligand-Fas pathway appears to be less important. Recombinant eosinophil cationic protein induced mainly necrosis of ECs. Furthermore, we demonstrated in situ apoptotic features of ECs in bronchial biopsy specimens of asthmatic patients. Conclusion: T cell- and eosinophil-induced apoptosis represents a key pathogenic event leading to EC shedding in asthma.

【 授权许可】

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