Utility of Animal Models in the Study of Human Airway Disease: Experimental Models (Part 7)
Ciliary dysfunction is another possible cause of impaired mucociliary interaction. In contrast to epithelial secretion, ciliary activity has been shown to respond inconsistently to inflammatory stimuli. While serum protein, eosinophil major basic protein, and adenosine have been found to inhibit ciliary activity in rabbits, guinea pigs and lower animals, the leukotrienes C4, D4 and the prostaglandins E, and E2 appear to stimulate ciliary beat frequency in sheep. Cilioinhibition would be expected to decrease and ciliostimulation to increase mucociliary transport.
The interrelationship among the various components of mucociliary interaction has been examined in allergic sheep. In this model, antigen challenge reduced tracheal mucociliary transport rate, an effect which was prevented by pretreatment with cromolyn sodium suggesting the involvement of inflammatory mediators in its pathogenesis. In vitro studies utilizing tracheal cells or tissues showed that the acute antigen-induced slowing of mucociliary transport was associated with mucus and water hypersecretion but not with cilioinhibition; the secretory effects could be blocked or blunted by pretreatment with cromolyn sodium, a glucocorticosteriod and a sulfidopeptide-leukotriene antagonist. levitra super active plus
Exogenous leukotriene D4 stimulated radiolabeled macromolecule and water secretions and decreased mucociliary clearance in the trachea. From these results, it was concluded that in allergic sheep, antigen-induced mucociliary dysfunction is related to the release of inflammatory mediators (eg, sulfidopeptide-leukotrienes) and was due primarily to an abnormality in epithelial secretion. It remains to be shown if immunologically-induced airway secretory dysfunction is also present in other animal models and what the nature of the respective inflammatory mediators might be.