Oxidative and nitrosative events in asthma.
Asthma affects over 15 million individuals in the United States, with over 1.5 million emergency room visits, 500,000 hospitalizations, and 5500 deaths each year, many of which are children. Airway inflammation is the proximate cause of the recurrent episodes of airflow limitation in asthma. Research applying molecular biology, chemistry, and cell biology to human asthma and model systems of asthma over the last decade has revealed that numerous biologically active proinflammatory mediators lead to increased production of reactive oxygen species (ROS) and the gaseous molecule nitric oxide (NO). Persistently increased ROS and NO in asthma lead to reactive nitrogen species (RNS) formation and subsequent oxidation and nitration of proteins, which may cause alterations in protein function that are biologically relevant to airway injury/inflammation. Eosinophil peroxidase and myeloperoxidase, leukocyte-derived enzymes, amplify oxidative events and are another enzymatic source of NO-derived oxidants and nitrotyrosine formation in asthma. Concomitant with increased generation of oxidative and nitrosative molecules in asthma, loss of protective antioxidant defense, specifically superoxide dismutase (SOD), contributes to the overall toxic environment of the asthmatic airway. This review discusses the rapidly accruing data linking oxidative and nitrosative events as critical participants in the acute and chronic inflammation of asthmatic airways.
Andreadis
Athena A
AA
Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Hazen
Stanley L
SL
Comhair
Suzy A A
SA
Erzurum
Serpil C
SC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001249:Asthma / Q000473:pathology* / Q000628:therapy; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000378:metabolism; D005609:Free Radicals; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide; D009584:Nitrogen / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D014443:Tyrosine; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D013482:Superoxide Dismutase; D009584:Nitrogen; D010100:Oxygen