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)