MURINE PULMONARY CA2-TRANSPORT SYSTEM ACTIVATED BY ALLERGIC IMMUNE-RESPONSE RETAINS SENSITIVITY TO OXIDATIVE STRESS()

Exaggerated oxygen radical production by airway cells may contribute t o increased airway responsiveness and heightened smooth muscle constri ction in asthmatic lungs. Smooth muscle cell contractility in the lung is regulated by Ca2+ homeostasis. The contribution of inflammatory ce lls to these events is unclear. A murine model of allergic pulmonary h ypersensitivity was developed to study the role of Ca2+ transport in a llergic pulmonary reactions. Sensitization of mice was accomplished by injection with ovalbumin (OA) (1 or 50 mu g) or OA (1 mu g) plus Al(O H)(3). Pulmonary responses were elicited by inhalation provocation cha llenge with OA aerosol and quantified by the extent of inflammatory ce ll infiltrate at 24 h. Increased Ca2+ transport was found in microsome s and homogenates of the lung after antigen challenge. Activation of C a2+ transport was correlated with the severity of the allergic pulmona ry response as evidenced from specific antibody production and inflamm atory cell infiltrate. The greatest increase in Ca2+ transport was not ed in microsomes from mice sensitized with OA plus adjuvant. Ca2+. tra nsport in sensitized, but not in control mice, was responsive to oxida tive stress induced by addition of phenol and hydrogen peroxide. Lung homogenates from both groups of animals responded similarly to phenoxy l radical-induced oxidative stress induced by phenol plus exogenous ty rosinase. These results are the first to indicate heightened Ca2+ tran sport in pulmonary microsomes following an allergic lung response and emphasize the role of aluminum hydroxide in enhancing allergic reactio ns in the lung The responsiveness of the system to oxidative stress su ggests that oxidative mechanisms may contribute to the physiologic and pathologic manifestations, such as airway hyperreactivity, associated with allergic pulmonary disease.