In vivo effects of apoptosis in asthma examined by a marine model

Background: One of the characteristic features of bronchial asthma is the a ccumulation of various inflammatory cells, predominantly eosinophils, at th e subepithelial region beneath the basement membrane of the airway. Apoptos is is a form of physiological cell death, through which the cellular conten ts including biologically active substances are kept in the cell membrane a nd are removed without their harmful effects. So, attempts were made to cla rify whether the induction of apoptosis is beneficial in asthma by using a murine model with ovalbumin (OA) as responsible allergen. Methods: A/J mice , which are genetically predisposed to be hyperresponsive to acetylcholine, were immunized with OA and alum, accompanied by OA inhalation for 2 weeks, during which some of the mice were also treated with either anti-fas monoc lonal antibody or sham control hamster IgG intranasally, Airway responsiven ess to acetylcholine was then analyzed by measuring airway resistance with a body plethysmograph box. Apoptosis was assessed by propidium iodide and T UNEL staining. Results: Inhalation of OA increased both airway responsivene ss to acetylcholine and the number of cells, mostly eosinophils, infiltrate d into the airway. Administration of anti-fas antibody induced apoptosis in the infiltrated eosinophils and abolished augmentation of airway hyperresp onsiveness caused by OA inhalation. Conclusion: Induction of apoptosis in p roinflammatory cells including eosinophils at the airway may have a benefic ial effect on suppressing airway hyperresponsiveness. Copyright (C) 2001 S. Karger AG, Basel.