Airway Mucus: Composition and Regulation of its Secretion by Neuropeptides in vitro

Abstract

Human and canine airway mucosa in vitro synthesizes and secretes mucus glycoprotein, proteoglycans and lipids which can be separated by density gradient ultracentrifugation in caesium bromide. In secretions from unstimulated explants, the small amount of mucus glycoprotein present is found in association with proteoglycans. 'Free' mucus glycoprotein of typical buoyant density is present only after stimulation of submucosal gland secretion by methacholine. Lipids are synthesized, at least in part, by the airway mucosa and occur in explant secretions as a viscoelastic gel, suggesting that they significantly influence the rheological properties of airway mucus. In addition to cholinergic and adrenergic secretomotor neurons, the airway mucosa is innervated by peptidergic fibres containing immunoreactivity to vasoactive intestinal peptide (VIP) and substance P (SP). In explants of non-bronchitic human airway, VIP inhibits baseline glycoprotein and lysozyme secretion; in canine airway mucosa, by contrast, VIP is a weak partial secretory agonist. SP is the most potent agonist of canine airway glycoprotein release described to date and appears to evoke secretion by a direct action on a stereospecific SP receptor rather than by inducing release of other endogenous secretagogues. VIP and SP have little effect on glycoprotein discharge by mucous and serous cells of the submucosal gland; SP appears to induce secretion by causing contraction of submucosal gland ducts. This may represent the most rapid way for delivering mucus into the airway in response to injury or irritation of airway epithelium.