INDUCTION OF NITRIC-OXIDE SYNTHASE IN A MODEL OF ALLERGIC OCCUPATIONAL ASTHMA

We have studied the induction of nitric oxide during late allergic res ponses, using a guinea pig model of trimellitic anhydride (TMA)-induce d airway allergy. TMA is a low molecular weight chemical which can cau se occupational asthma. The activity of nitric oxide synthase (NOS) wa s investigated by the detection of H-3-labeled citrulline formation fr om 3H-labeled arginine. In sensitized animals, challenge with TMA conj ugated to guinea pig albumin (TMA-GPSA) increased the activity of Ca2-independent NOS (inducible NOS; iNOS) in lung and bronchial tissues a t 15-17 h after challenge compared to nonsensitized animals. The induc tion of iNOS activity was associated with an increased level of nitrit e, an end metabolite of the 1-arginine-NO pathway, in bronchoalveolar lavage fluid. In contrast to iNOS, the activity of Ca2+-dependent NOS (constitutive NOS; cNOS) was not affected by the allergen challenge. T hese results demonstrate that iNOS in bronchial tissue is induced late after allergen challenge in sensitized guinea pig.