Upper respiratory infections (URIs) commonly precipitate an attack of asthma. Viruses are the cause of the majority of these episodes. It is not known how viruses lead to increased asthma. Airway hyperirritability is a fundamental defect in asthma. During virus URIs airway smooth muscle reactivity is markedly increased. To study this problem we have developed and utilized an animal model (parainfluenza 3 infected, ovalbumin sensitized guinea pigs) and isolated human leukocytes. Preliminary studies have found and abnormality in leukocyte responsiveness suggesting defect in membrane permeability to calcium. From these observations, we have hypothesized that viruses alter calcium membrane permeability and this is reflected in both leukocyte function and airway smooth muscle reactivity. This proposal is designed to examine these effects by (1) assaying the effects of in vivo viral infections and in vitro influenza A incubations upon basophilic leukocyte histamine release (HR) and its modulation by antagonists of calcium movement and metabolism; (2) assaying the above viral effects on polymorphonuclear (PMN) leukocyte function (oxygen consumption, superoxide generation, chemiluminescence, and lysosomal enzyme release) and its modulation by antagonists of calcium movement and metabolism; (3) assaying airway smooth muscle (trachea, bronchus, and parenchymal strips) function parainfluenza 3 infected and non-infected guinea pigs and modulation by calcium antagonists; and (4) assaying basophilic and polymorphonuclear leukocyte function in cells from the guinea pig model along with a comparison to changes in airway function.
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