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Am. J. Respir. Crit. Care Med., Volume 158, Number 4, October 1998, 1127-1133

Involvement of alpha -4 Integrins in Allergic Airway Responses and Mast Cell Degranulation In Vivo

MASAYUKI HOJO, KARIM MAGHNI, THOMAS B. ISSEKUTZ, and JAMES G. MARTIN

Meakins-Christie Laboratories, McGill University, Montreal, Quebec; and the Izaak Walton Killam Children's Hospital, Grace Centre, Dalhousie University, Halifax, Nova Scotia, Canada

Antibodies against integrins have been shown to inhibit allergic airway responses. The purpose of this study was to test the hypothesis that the beta 1 integrin, very late antigen-4 (VLA-4), is involved in mast cell activation triggered by allergen exposure in sensitized animals. To do this we studied Brown Norway rats that were sensitized to ovalbumin (OA; 1 mg subcutaneously) using Bordetella pertussis as an adjuvant. Two weeks later rats were challenged with OA, pulmonary resistance (RL) was determined, and the concentrations of histamine and tryptase in bronchoalveolar lavage fluid and N-acetyl-leukotriene (LT)E4 in bile were measured. Pretreatment with a monoclonal antibody against VLA-4 (TA-2) attenuated the early response after OA challenge (342.9 ± 24.4% baseline RL versus 153.3 ± 19.4%; p < 0.01). There were significantly lower concentrations of histamine (67.11 ± 11.90 µg/ml versus 26.69 ± 1.84; p < 0.01) and tryptase (0.143 ± 0.035 µg/ml versus 0.053 ± 0.022 µg/ml; p < 0.01) in TA-2-treated animals. The increases in the concentrations of biliary N-acetyl-LTE4 after OA challenge were also significantly lower in TA-2-treated animals. These data suggest that a selective anti-VLA-4 monoclonal antibody prevents early responses through inhibition of mast cell activation.




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