DECREASED CU,ZN-SOD ACTIVITY IN ASTHMATIC AIRWAY EPITHELIUM - CORRECTION BY INHALED CORTICOSTEROID IN-VIVO

To investigate the antioxidant response of respiratory epithelium to t he chronic airway inflammation in asthma, the major intracellular anti oxidants [copper and zinc-containing superoxide dismutase (Cu,Zn-SOD) and manganese-containing SOD (Mn-SOD), catalase, and glutathione perox idase] were quantitated in bronchial epithelial cells of healthy contr ol and asthmatic individuals. Although catalase and glutathione peroxi dase in bronchial epithelium of asthmatics were similar to control, SO D activity in asthmatics not on inhaled corticosteroid (-CS) was lower than asthmatics on inhaled corticosteroid (+CS) and controls. Investi gation of Mn-SOD and Cu,Zn-SOD activities revealed that the lower SOD activity in asthmatics -CS was because of decreased Cu,Zn-SOD activity . However, Mn-SOD and Cu,Zn-SOD mRNA and protein levels were similar a mong asthmatics -CS, asthmatics +CS, and controls. Importantly, Cu,Zn- SOD specific activity in asthmatics -CS was decreased in comparison wi th control and asthmatics +CS. Furthermore, in paired comparisons of a sthmatics -CS and +CS, inhaled corticosteroids resulted in normalizati on of bronchial epithelial Cu,Zn-SOD specific activity. These findings suggest loss of Cu,Zn-SOD activity in asthma is related to inflammati on, perhaps through oxidant inactivation of Cu,Zn-SOD protein.