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

We have studied the induction of nitric oxide during late allergic responses, using a guinea pig model of trimellitic anhydride (TMA)-induced airway allergy. TMA is a low molecular weight chemical which can cause occupational asthma. The activity of nitric oxide synthase (NOS) was investigated by the detection of H-3-labeled citrulline formation from 3H-labeled arginine. In sensitized animals, challenge with TMA conjugated to guinea pig albumin (TMA-GPSA) increased the activity of Ca2+-independent NOS (inducible NOS; iNOS) in lung and bronchial tissues at 15-17 h after challenge compared to nonsensitized animals. The induction of iNOS activity was associated with an increased level of nitrite, 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. These results demonstrate that iNOS in bronchial tissue is induced late after allergen challenge in sensitized guinea pig.