Murine pulmonary Ca(2+)-transport system activated by allergic immune response retains sensitivity to oxidative stress.

Abstract

Exaggerated oxygen radical production by airway cells may contribute to increased airway responsiveness and heightened smooth muscle constriction in asthmatic lungs. Smooth muscle cell contractility in the lung is regulated by Ca2+ homeostasis. The contribution of inflammatory cells to these events is unclear. A murine model of allergic pulmonary hypersensitivity was developed to study the role of Ca2+ transport in allergic pulmonary reactions. Sensitization of mice was accomplished by injection with ovalbumin (OA) (1 or 50 micrograms) or OA (1 microgram) plus Al(OH)3. Pulmonary responses were elicited by inhalation provocation challenge with OA aerosol and quantified by the extent of inflammatory cell infiltrate at 24 h. Increased Ca2+ transport was found in microsomes and homogenates of the lung after antigen challenge. Activation of Ca2+ transport was correlated with the severity of the allergic pulmonary response as evidenced from specific antibody production and inflammatory cell infiltrate. The greatest increase in Ca2+ transport was noted in microsomes from mice sensitized with OA plus adjuvant. Ca2+ transport in sensitized, but not in control mice, was responsive to oxidative stress induced by addition of phenol and hydrogen peroxide. Lung homogenates from both groups of animals responded similarly to phenoxyl radical-induced oxidative stress induced by phenol plus exogenous tyrosinase. These results are the first to indicate heightened Ca2+ transport in pulmonary microsomes following an allergic lung response and emphasize the role of aluminum hydroxide in enhancing allergic reactions in the lung. The responsiveness of the system to oxidative stress suggests that oxidative mechanisms may contribute to the physiologic and pathologic manifestations, such as airway hyperreactivity, associated with allergic pulmonary disease.