Regulation of secretion from mucous and serous cells in the excised ferrettrachea

Mucus hypersecretion is an important characteristic of many airway diseases . Mucin is the major component of mucus, and is secreted from surface goble t cells of the airway epithelium and mucous cells of submucosal glands. Lys ozyme is an enzyme secreted by serous cells of airway submucosal glands. We hypothesized that secretagogues acting through different pathways would ha ve different effects on tracheal mucin and lysozyme secretion. We used a sa ndwich enzyme-linked lectin assay (ELLA) to measure mucin-like glycoprotein secretion and a spectrophotometric method to measure lysozyme secretion fr om isolated ferret tracheal segments. We evaluated the secretory response t o four secretagogues; prostaglandin F-2 alpha (PGF(2 alpha)), adenosine tri phosphate (ATP), methacholine (MCh), and human neutrophil elastase (HNE). E ach agent stimulated mucin and lysozyme secretion. The relative potency was PGF(2 alpha) less than or equal to ATP < MCh < HNE for mucin and ATP less than or equal to PGF(2 alpha) < MCh < HNE for lysozyme secretion. We showed that there is an anatomic gradient for constitutive and stimulated mucin a nd lysozyme secretion with the distal tracheal segments secreting more muci n and lysozyme per gram of tissue than the proximal segments. This robust m odel system can be used to evaluate the regulation of airway mucous and ser ous cell secretion and to assess the effect of agents that might alter the secretory response. We confirm that on an equimolar basis, HNE is one of th e most potent mucus secretagogues. (C) 2001 Elsevier Science B.V. All right s reserved.