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Apoptosis and expression of Fas (CD95) and Fas ligand (CD95L) in the airways of severe asthma subjects Chagani, Tabassum

Abstract

Airway epithelial denudation is characteristic of asthma and may contribute to non-specific bronchial hyperresponsiveness and airway remodeling. Apoptotic pathway in these cells is mediated by Fas-FasL interaction. Loss of the protective immune function by FasL could permit prolonged survival of inflammatory cells in the airway mucosa. We postulated that 1) the process of epithelial apoptosis is enhanced in asthma, 2) there is decreased epithelial expression of FasL which may contribute to the persistence of inflammatory cells in the airway walls of asthma subjects. We performed the TUNEL assay to detect the extent of apoptosis, and immunohistochemical staining to determine the expression of Fas and FasL in asthmatic airways. Formalin fixed paraffin embedded airway sections from 17 severe asthma subjects, 16 chronic asthma subjects and 18 control subjects were studied. Images of the conducting airways were captured using a Spot Cooled digital camera linked to a computer. Quantification for TUNEL and immunohistochemical staining was performed using Image Pro-Plus® software. Epithelial apoptosis was increased in the severe asthma versus chronic asthma and control groups (p = 0.0004 all airways; p = 0.01 cartilaginous airways; p = 0.004 membranous airways). Epithelial expression of Fas and FasL was increased in the severe asthma group compared to chronic asthma and control groups (p = 0.04 and 0.0004 respectively for all airways combined). There was no difference in epithelial Fas expression between the groups when cartilaginous and membranous airways were analyzed separately. Epithelial FasL expression was increased in the severe asthma group in both the cartilaginous and membranous airways compared to chronic asthma and control groups (p = 0.0004 and 0.0008 respectively). Fas expressing inflammatory cells in the wall of membranous airways were increased in the severe asthma versus chronic asthma and control groups. There was no statistically significant difference between the study groups in FasL expressing inflammatory cells in the airway wall compartments. We demonstrate that there is increased apoptosis and epithelial expression of Fas and FasL in the airways of severe asthma group. Alteration in Fas or FasL expression does not contribute to persistence of asthma inflammation but could contribute to epithelial apoptosis.

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