ASBESTOS INHALATION INDUCES REACTIVE NITROGEN SPECIES AND NITROTYROSINE FORMATION IN THE LUNGS AND PLEURA OF THE RAT

To determine whether asbestos inhalation induces the formation of reac tive nitrogen species, three groups of rats were exposed intermittentl y over 2 wk to either filtered room air (sham-exposed) or to chrysotil e or crocidolite asbestos fibers. The rats were killed at 1 or 6 wk af ter exposure. At 1 wk, significantly greater numbers of alveolar and p leural macrophages from asbestos-exposed rats than from sham-exposed r ats demonstrated inducible nitric oxide synthase protein immunoreactiv ity. Alveolar macrophages from asbestos-exposed rats also generated si gnificantly greater nitrite formation than did macrophages from sham-e xposed rats. Strong immunoreactivity for nitrotyrosine, a marker of pe roxynitrite formation, was evident in lungs from chrysotile- and croci dolite-exposed rats at 1 and 6 wk. Staining was most evident at alveol ar duct bifurcations and within bronchiolar epithelium, alveolar macro phages, and the visceral and parietal pleural mesothelium. Lungs from sham-exposed rats demonstrated minimal immunoreactivity for nitrotyros ine, Significantly greater quantities of nitrotyrosine were detected b y ELISA in lung extracts from asbestos-exposed rats than from sham-exp osed rats. These findings suggest that asbestos inhalation can induce inducible nitric oxide synthase activation and peroxynitrite formation in vivo, and provide evidence of a possible alternative: mechanism of asbestos-induced injury to that thought to.be induced by Fenton react ions.