title: Antiinflammatory properties of inducible nitric oxide synthase in acute hyperoxic lung injury.
abstract: The objective of this study was to determine whether endogenous nitric oxide (NO), specifically the inducible NO synthase isoform (iNOS: NOS II), reduces or amplifies lung injury in mice breathing at a high oxygen tension. Previous studies have shown that exogenous (inhaled) NO protects against hyperoxia-induced lung injury, and that endogenous NO derived from iNOS inhibits leukocyte recruitment and protects against lung injury induced by lipopolysaccharide. In the present study, hyperoxia (> 98% O(2) for 72 h) induced acute lung injury in both wild-type and iNOS-deficient mice as determined by elevated albumin and lactate dehydrogenase levels in bronchoalveolar lavage fluid (BALF) and by increased extravascular lung water. Lung injury was greater in iNOS-deficient mice than in wild-type mice and was associated with an increased number of polymorphonuclear leukocytes in BALF. iNOS messenger RNA expression levels increased in the lungs of wild-type hyperoxic mice. Nitrotyrosine, a marker of reactive NO species, was expressed in both wild-type and iNOS-deficient mice in hyperoxia, indicating an iNOS-independent pathway for protein nitration. We conclude that iNOS is capable of reducing pulmonary leukocyte accumulation and lung injury. The data indicate that iNOS induction serves as a protective mechanism to minimize the effects of acute exposure to hyperoxia.
authors: Department of Medicine, Kitasato University School of Medicine, Kanagawa, Japan. hiro@kitasato-u.ac.jp
authors: H
authors: H
authors: Kobayashi
authors: R
authors: R
authors: Hataishi
authors: H
authors: H
authors: Mitsufuji
authors: M
authors: M
authors: Tanaka
authors: M
authors: M
authors: Jacobson
authors: T
authors: T
authors: Tomita
authors: W M
authors: WM
authors: Zapol
authors: R C
authors: RC
authors: Jones
mesh_terms: D000208:Acute Disease; D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D018496:Hyperoxia / Q000276:immunology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II; D009929:Organ Size; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014867:Water
chemical_list: D000418:Albumins; D014867:Water; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse