In vivo effects of apoptosis in asthma examined by a murine model.
BACKGROUND
One of the characteristic features of bronchial asthma is the accumulation of various inflammatory cells, predominantly eosinophils, at the subepithelial region beneath the basement membrane of the airway. Apoptosis is a form of physiological cell death, through which the cellular contents including biologically active substances are kept in the cell membrane and are removed without their harmful effects. So, attempts were made to clarify 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 monoclonal antibody or sham control hamster IgG intranasally. Airway responsiveness to acetylcholine was then analyzed by measuring airway resistance with a body plethysmograph box. Apoptosis was assessed by propidium iodide and TUNEL staining.


RESULTS
Inhalation of OA increased both airway responsiveness to acetylcholine and the number of cells, mostly eosinophils, infiltrated into the airway. Administration of anti-Fas antibody induced apoptosis in the infiltrated eosinophils and abolished augmentation of airway hyperresponsiveness caused by OA inhalation.


CONCLUSIONS
Induction of apoptosis in proinflammatory cells including eosinophils at the airway may have a beneficial effect on suppressing airway hyperresponsiveness.
Ohta
K
K
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. kenohta@med.teikyo-u.ac.jp
Yamashita
N
N
Tajima
M
M
Miyasaka
T
T
Kawashima
R
R
Nakano
J
J
Arioka
H
H
Ishii
A
A
Horiuchi
T
T
Miyamoto
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000485:Allergens / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D001249:Asthma / Q000276:immunology / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology; D004802:Eosinophilia / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; D019014:fas Receptor; D010047:Ovalbumin; D000109:Acetylcholine