K. Setoguchi et al., EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE AND ITS INVOLVEMENT IN PULMONARY GRANULOMATOUS INFLAMMATION IN RATS, The American journal of pathology, 149(6), 1996, pp. 2005-2022
Two types of pulmonary granulomatosis were produced in rats by intratr
acheal instillation of zymosan or silica. In both models, immunostaini
ng with anti-mt monoclonal antibody for inducible nitric oxide synthas
e (iNOS), ANOS11, showed that the intensity of iNOS immunoreactivity i
n the inflammatory lesions peaked at 3 days and declined thereafter, I
mmunohistochemical double staining and in situ hybridization demonstra
ted the expression of iNOS is neutrophils, monocyte-derived macrophage
s, and bronchiolar epithelial cells in the pulmonary lesions, Electron
spin resonance spectroscopy revealed the production of an excessive a
mount of nitric oxide (NO) in the pulmonary lesions, Immunostaining wi
th a polyclonal antibody against nitrotyrosine indicated the formation
of nitrotyrosine residues in the granulomatous lesions, particularly
in the periphery of the lesions, providing indirect evidence for the g
eneration of peroxynitrite anion in the zymosan- or silica-instilled l
ungs Administration of N-omega-nitro-L-arginine nine methyl ester or S
-methylisothiourea sulfate, which significantly suppressed NO producti
on, resulted in marked reduction of monocyte/macrophage infiltration a
s well as in inhibition of induction of monocyte chemoattractant prote
in-1 in the lesions These data indicate that NO and its more reactive
product peroxynitrite anion may be important mediators of granuloma fo
rmation in the lung.