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 respirator y airways are uniquely vulnerable regarding potential for oxidative da mage due to their potential for exposure to both endogenous (e.g., mit ochondrial respiration, phagocytic respiratory burst, cellular oxidase s) 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 ins ult. Nonenzymatic defenses include certain vitamins and low molecular weight compounds such as thiols. The enzymes superoxide dismutase, cat alase, and glutatione peroxidase are major sources of antioxidant prot ection. Other materials associated with airway epithelium such as mucu s, epithelial lining fluid, and even the basement membrane/extracellul ar 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 co mponent in the pathogenesis of several respiratory diseases. Oxidant s tress may profoundly alter lung physiology including pulmonary functio n (e.g., forced expiratory volumes, flow rates, and maximal inspirator y capacity), mucociliary activity, and airway reactivity. ROS may indu ce airway inflammation; the inflammatory process may serve as an addit ional source oi ROS in airways and provoke the pathophysiologic respon ses 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 m ay be intimately involved in defense against, and pathophysiologic cha nges invoked by, ROS.