Interactions of oxygen radicals with airway epithelium.
Reactive oxygen species (ROS) have been implicated in the pathogenesis of numerous disease processes. Epithelial cells lining the respiratory airways are uniquely vulnerable regarding potential for oxidative damage due to their potential for exposure to both endogenous (e.g., mitochondrial respiration, phagocytic respiratory burst, cellular oxidases) and exogenous (e.g., air pollutants, xenobiotics, catalase negative organisms) oxidants. Airway epithelial cells use several nonenzymatic and enzymatic antioxidant mechanisms to protect against oxidative insult. Nonenzymatic defenses include certain vitamins and low molecular weight compounds such as thiols. The enzymes superoxide dismutase, catalase, and glutatione peroxidase are major sources of antioxidant protection. Other materials associated with airway epithelium such as mucus, epithelial lining fluid, and even the basement membrane/extracellular matrix may have protective actions as well. When the normal balance between oxidants and antioxidants is upset, oxidant stress ensues and subsequent epithelial cell alterations or damage may be a critical component in the pathogenesis of several respiratory diseases. Oxidant stress may profoundly alter lung physiology including pulmonary function (e.g., forced expiratory volumes, flow rates, and maximal inspiratory capacity), mucociliary activity, and airway reactivity. ROS may induce airway inflammation; the inflammatory process may serve as an additional source of ROS in airways and provoke the pathophysiologic responses described. On a more fundamental level, cellular mechanisms in the pathogenesis of ROS may involve activation of intracellular signaling enzymes including phospholipases and protein kinases stimulating the release of inflammatory lipids and cytokines. Respiratory epithelium may be intimately involved in defense against, and pathophysiologic changes invoked by, ROS.
Wright
D T
DT
Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University, College of Veterinary Medicine, Raleigh 27606.
Cohn
L A
LA
Li
H
H
Fischer
B
B
Li
C M
CM
Adler
K B
KB
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology
D000975:Antioxidants; D017382:Reactive Oxygen Species; D010088:Oxidoreductases