Role of VLA-4 and LFA-1 in allergen-induced airway hyperresponsiveness and lung inflammation in the rat.
The aim of the study was to evaluate the effects of blocking the integrins VLA-4 and LFA-1 on allergen-induced airway eosinophilia and responsiveness in Brown-Norway rats. Ovalbumin-sensitized rats were exposed to either aerosols of ovalbumin or saline. Airway responsiveness to methacholine (MCh) was determined 8 and 32 h after challenge. Cellular populations in the lung lavage and lung tissues were determined 32 h after allergen challenge. Total numbers of eosinophils were increased in the lung lavage (25 ml) and the small airways/parenchyma in the ovalbumin (OA)-challenged rats (4.37 x 10(6) +/- 0.71 and 15.54 x 10(6) +/- 1.99, respectively) compared with the saline-challenged rats (0.99 x 10(6) +/- 0.81 and 4.84 x 10(6) +/- 2.27; p < 0.05). Animals treated with both anti-VLA-4 and anti-LFA-1 mAbs and with anti-LFA-1 mAb alone had reduced numbers of eosinophils in the lung lavage (0.76 x 10(6) +/- 0.80 and 0.40 x 10(6) +/- 1.14, respectively; p < 0.05) and in the small airways/parenchyma (8.64 x 10(6) +/- 2.07 and 4.44 x 10(6) +/- 3.20; p < 0.05). Anti-VLA-4 mAb treatment alone did not alter the eosinophils recovered from the lung. Airway responsiveness to methacholine increased from 8 to 32 h in all ovalbumin-challenged rats, but treatment with anti-VLA-4, anti-LFA-1, or both mAbs prevented the increase in responsiveness. In conclusion, allergen-induced airway hyperresponsiveness is inhibitable by blocking either VLA-4 or LFA-1 integrins and is associated with a lung eosinophilia that is LFA-1 dependent and VLA-4 independent.(ABSTRACT TRUNCATED AT 250 WORDS)
Laberge
S
S
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Rabb
H
H
Issekutz
T B
TB
Martin
J G
JG
D000818:Animals; D000911:Antibodies, Monoclonal; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007958:Leukocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D011914:Rats, Inbred BN; D016029:Receptors, Very Late Antigen / Q000276:immunology / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen; D016210:Methacholine Chloride; D010047:Ovalbumin