In the present study, we investigated the role of inducible (or type 2)
nitric oxide synthase (iNOS) in the development of acute
inflammation by comparing the responses in wild-type mice (WT) and mice lacking (knockout [KO]). When compared with
carrageenan-treated iNOS-WT mice, iNOS-KO mice that had received
carrageenan exhibited a reduced degree of pleural exudation and polymorphonuclear cell migration. Lung
myeloperoxidase (MPO) activity and lipid peroxidation were significantly reduced in iNOS-KO mice in comparison with iNOSWT mice. Immunohistochemical analysis for
nitrotyrosine revealed positive staining in lungs from
carrageenan-treated iNOS-WT mice. Lung tissue sections from
carrageenan-treated iNOS-WT mice showed positive staining for poly
adenosine diphosphate (
ADP)-ribose synthetase that was mainly localized in alveolar macrophages and in airway epithelial cells. The intensity and degree of staining for
nitrotyrosine and
poly-ADP-ribose synthetase were markedly reduced in tissue sections from
carrageenan-treated iNOS-KO mice. The inflamed lungs of iNOS-KO mice also showed an improved histologic status. Furthermore, a significant reduction in the suppression of energy status, in
DNA strand breakage, and in decreased cellular levels of
nicotinamide adenine dinucleotide (
NAD(+)) was observed ex vivo in macrophages harvested from the pleural cavity of iNOS-KO mice subjected to
carrageenan-induced
pleurisy. Taken together, our results clearly show that iNOS plays an important role in the acute inflammatory response.