Cystic fibrosis and the relationship between mucin and chloride secretion by cultures of human airway gland mucous cells.

Finkbeiner WE, Zlock LT, Morikawa M, Lao AY, Dasari V, Widdicombe JH. Cystic fibrosis and the relationship between mucin and chloride secretion by cultures of human airway gland mucous cells. Am J Physiol Lung Cell Mol Physiol 301: L402-L414, 2011. First published July 1, 2011; doi: 10.1152/ajplung.00210.2010.-We investigated how cystic fibrosis (CF) alters the relationship between Cl- and mucin secretion in cultures of non-CF and CF human tracheobronchial gland mucous (HTGM and CFTGM, respectively) cells. Biochemical studies showed that HTMG cells secreted typical airway mucins, and immunohistochemical studies showed that these cells expressed MUC1, MUC4, MUC5B, MUC8, MUC13, MUC16, and MUC20. Effects of cumulative doses of methacholine (MCh), phenylephrine (Phe), isoproterenol (Iso), and ATP on mucin and Cl- secretion were studied on HTGM and CFTGM cultures. Baseline mucin secretion was not significantly altered in CFTGM cells, and the increases in mucin secretion induced by mediators were unaltered (Iso, Phe) or slightly decreased (MCh, ATP). Across mediators, there was no correlation between the maximal increases in Cl- secretion and mucin secretion. In HTGM cells, the Cl- channel blocker, diphenylamine-2-carboxylic acid, greatly inhibited Cl- secretion but did not alter mucin release. In HTGM cells, mediators (10(-5) M) increased mucin secretion in the rank order ATP > Phe = Iso > MCh. They increased Cl- secretion in the sequence ATP > MCh approximate to Iso > Phe. The responses in Cl- secretion to MCh, ATP, and Phe were unaltered by CF, but the response to Iso was greatly reduced. We conclude that mucin secretion by cultures of human tracheobronchial gland cells is independent of Cl- secretion, at baseline, and is unaltered in CF; that the ratio of Cl- secretion to mucus secretion varies markedly depending on mediator; and that secretions induced by stimulation of beta-adrenergic receptors will be abnormally concentrated in CF.