title: Inducible nitric oxide synthase-knockout mice exhibit resistance to pleurisy and lung injury caused by carrageenan.
abstract: 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.
authors.affiliation: Institute of Pharmacology and Department of Biomorphology School of Medicine, University of Messina, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: E
authors.initials: E
authors.lastname: Mazzon
authors.forename: G
authors.initials: G
authors.lastname: Calabro
authors.forename: L
authors.initials: L
authors.lastname: Dugo
authors.forename: A
authors.initials: A
authors.lastname: De Sarro
authors.forename: F A
authors.initials: FA
authors.lastname: van De LOO
authors.forename: A P
authors.initials: AP
authors.lastname: Caputi
mesh_terms: D000818:Animals; D002351:Carrageenan; D002478:Cells, Cultured; D004249:DNA Damage; D004789:Enzyme Activation; D005122:Exudates and Transudates / Q000737:chemistry / Q000166:cytology; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D010994:Pleura / Q000473:pathology; D010998:Pleurisy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D002351:Carrageenan; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011065:Poly(ADP-ribose) Polymerases