S. Tanaka et al., ASBESTOS INHALATION INDUCES REACTIVE NITROGEN SPECIES AND NITROTYROSINE FORMATION IN THE LUNGS AND PLEURA OF THE RAT, The Journal of clinical investigation, 102(2), 1998, pp. 445-454
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.