INHALATION OF TOLUENE DIISOCYANATE IS ASSOCIATED WITH INCREASED PRODUCTION OF NITRIC-OXIDE BY RAT BRONCHOALVEOLAR LAVAGE CELLS

Isocyanates are used commercially, particularly in the manufacture of polyurethane coatings and foam. These compounds can pose an occupation al health hazard since there is a risk of respiratory disease followin g isocyanate exposure. The purpose of the present study was to investi gate whether a single, sublethal isocyanate inhalation is associated w ith increased production of the free radical nitric oxide (NO). Mature male Sprague-Dawley rats were exposed to air or toluene diisocyanate (TDI; 2 ppm) for 4 hr. Indices of pulmonary function were assessed bef ore and after exposure to TDI fumes. At 20 hr postexposure, bronchoalv eolar lavage cells (BALC) and fluid were harvested. NO synthase (NOS)- dependent reactive species production by alveolar macrophages was asse ssed by determining N omega-nitro-L-arginine methyl ester-inhibitable chemiluminescence following stimulation with unopsonized zymosan. Nort hern blot analysis was used to index inducible NOS mRNA levels in BALC , while nitrite and nitrate (NOx) levels were measured to determine NO x levels in the lavage fluid and the production of NO by cultured adhe rent BALC was indexed by measuring nitrite levels. Exposure to aerosol ized TDI was associated with an increase in the number of alveolar mac rophages, lymphocytes, and polymorphonuclear leukocytes harvested by b ronchoalveolar lavage, relative to that from air-exposed rats. NO, lev els in the lavage fluid and NOS-dependent production of reactive speci es by alveolar macrophages were increased following TDI exposure. In a ddition, inducible NO production by BALC (i.e., mRNA levels and nitrit e levels in BALC conditioned media) was elevated following TDI treatme nt. These findings indicate that pulmonary inflammatory responses indu ced by TDI exposure are associated with increases in inducible NO prod uction. Therefore, the potential role of NO in the initial pulmonary r esponse to TDI exposure warrants further investigation. (C) 1997 Acade mic Press.