Utility of Animal Models in the Study of Human Airway Disease: Experimental Models (Part 6)
These examples demonstrate that the different animal models of airway smooth muscle hyperresponsiveness involve different pathogenetic pathways. The animal studies therefore cannot answer the question of which of these mechanisms are also operative in humans with airway hyperresponsiveness. buy diabetes drugs
In patients with bronchial asthma, the airway epithelium secretes liquids at an increased rate and probably of abnormal rheologic properties, and removes the secreted liquids by ciliary activity at a diminished rate. The combination of hypersecretion and impaired mucociliary interaction is felt to be responsible for the accumulation of secretions in the airways. Since inflammation seems to play a critical role in the airway smooth muscle component of airway hyperresponsiveness, the effects of inflammatory products on airway epithelial function have also been studied extensively in animals.
The airway surface liquids consist of a gel (mucus) and a sol (periciliary fluid) produced by mucus cells and by epithelial ion and water transport. Lipoxygenase metabolites of arachidonic acid (15-hydroxyeico-satetraeonic acid, sulfidopeptide-leukotrienes, thromboxane A2 analogues, prostaglandin E, and E2), platelet activating factor, adenosine, and substance P have been shown to increase the secretion of mucus substances in different species.* In addition, serum exudation has the potential of stimulating mucus secretion in the airway. Inflammatory stimuli can also increase net ion, and hence, water transport across the airway epithelium towards the airway lumen thereby contributing to hypersecretion. Thus, histamine, several arachidonic acid metabolites, bradyki-nin, and substance P have been reported to increase chloride secretion by the canine tracheal epithelium.^ Eosinophil major basic protein, another inflammatory mediator, has been found to have similar effects. At least in the dog, prostaglandin Ex and E2 seem to be potent stimulators of chloride secretion and some of the other mediators may exert their action on chloride secretion by the generation of prostaglandin E( and E2.