ATP induced MUC5AC release from human airways in vitro

Background: Chronic airway diseases are often associated with marked mucus production, however, little is known about the regulation of secretory acti vity by locally re leas ed endogenous mediators. Aim: This investigation was performed to determine the release of MUC5AC mu cin from human bronchial preparations using the purinergic agonists adenosi ne 59-triphosphate (ATP) and uridine 5'-triphosphate (UTP). Methods : Immunohistochemical and immunoradiometric assays (IRMA) were used to detect the MUC5AC mucin. Immunohistochemical analysis were performed us ing individual 1-13 M1 and 21 M1 MAbs recognizing a recombinant M1 mucin pa rtially encoded by the MUC5AC gene. IRMA measurments were performed using a mixture of eight anti-M1 mucin MAbs (PM8), which included both 1-13 M1 and 21 M1 MAbs. Lysozyme and protein were also measured in the biological flui ds derived from human bronchial preparations obtained from patients who had undergone surgery for lung carcinoma. Results : The anti-M1 monoclonal antibodies labelled epithelial goblet cell s. After challenge of human bronchial preparations with ATP, the goblet cel ls exhibited less staining. In contrast, UTP did not alter the immunolabell ing of goblet cells. MUC5AC mucin in the bronchial fluids derived from ATP- challenged preparations was increased while UTP had no effect on release. A TP did not alter either the quantities of lysozyme or protein detected in t he biological fluids. Conclusion: These results suggest that ATP may regulate epithelial goblet c ell secretion of MUC5AC mucin fr om human air ways in vitro.