Contribution of reactive oxygen and nitrogen species to particulate-induced lung injury.
Recently, a second pathway for the generation of potential oxidants with the reactivity of the hydroxyl radical without the need for metal catalysis has been described. In response to various inflammatory stimuli, lung endothelial, alveolar, and airway epithelial cells, as well as activated alveolar macrophages, produce both nitric oxide (.NO) and superoxide anion radicals (O2.-). .NO regulates pulmonary vascular and airway tone and plays an important role in lung host defense against various bacteria. However, .NO may be cytotoxic by inhibiting critical enzymes such as mitochondrial aconitase and ribonucleotide reductase, by S-nitrosolation of thiol groups, or by binding to their iron-sulfur centers. In addition, .NO reacts with O2.- at a near diffusion-limited rate to form the strong oxidant peroxynitrite (ONOO-), which can nitrate and oxidize key amino acids in various lung proteins such as surfactant protein A, and inhibit their functions. The presence of ONOO- in the lungs of patients with acute respiratory distress syndrome has been demonstrated by measuring levels of nitrotyrosine, the stable product of tyrosine nitration. Various studies have shown that inhalation or intratracheal instillation of various respirable mineral dusts or asbestos fibers increased levels of inducible nitric oxide synthase mRNA. In this presentation, we review the evidence for the upregulation of .NO in the lungs of animals exposed to mineral particulates and assess the contribution of reactive nitrogen species in the pathogenesis of the resultant lung injury.
Zhu
S
S
Department of Anesthesiology, University of Alabama at Birmingham 35233-6810, USA.
Manuel
M
M
Tanaka
S
S
Choe
N
N
Kagan
E
E
Matalon
S
S
D000818:Animals; D001194:Asbestos / Q000633:toxicity; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D055370:Lung Injury; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D009566:Nitrates; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D001194:Asbestos; C039642:peroxynitric acid; D009569:Nitric Oxide; D009584:Nitrogen