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

被引:28
作者
Finkbeiner, Walter E. [1 ]
Zlock, Lorna T. [1 ]
Morikawa, Masatoshi [1 ]
Lao, Anna Y. [1 ]
Dasari, Vijay [1 ]
Widdicombe, Jonathan H. [2 ]
机构
[1] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94110 USA
[2] Univ Calif Davis, Dept Human Physiol, Davis, CA 95616 USA
基金
美国国家卫生研究院;
关键词
trachea; bronchi; mucus; ion transport; TRANSMEMBRANE CONDUCTANCE REGULATOR; TRACHEAL SURFACE EPITHELIUM; BRONCHIAL SUBMUCOSAL GLAND; SEROUS ACINAR-CELLS; FLUID SECRETION; GENE-EXPRESSION; GOBLET CELLS; TRACHEOBRONCHIAL GLANDS; ION-TRANSPORT; GLYCOPROTEINS;
D O I
10.1152/ajplung.00210.2010
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:L402 / L414
页数:13
相关论文
共 71 条
[1]   Dysfunction of mitochondria Ca2+ uptake in cystic fibrosis airway epithelial cells [J].
Antigny, Fabrice ;
Girardin, Nathalie ;
Raveau, Dorothee ;
Frieden, Maud ;
Becq, Frederic ;
Vandebrouck, Clarisse .
MITOCHONDRION, 2009, 9 (04) :232-241
[2]  
Argüeso P, 2002, INVEST OPHTH VIS SCI, V43, P1004
[3]   Liquid secretion inhibitors reduce mucociliary transport in glandular airways [J].
Ballard, ST ;
Trout, L ;
Mehta, A ;
Inglis, SK .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2002, 283 (02) :L329-L335
[4]   Fluid secretion by submucosal glands of the tracheobronchial airways [J].
Ballard, Stephen T. ;
Spadafora, Domenico .
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 2007, 159 (03) :271-277
[5]   Mucin gene expression during differentiation of human airway epithelia in vitro -: MUC4 and MUC5B are strongly induced [J].
Bernacki, SH ;
Nelson, AL ;
Abdullah, L ;
Sheehan, JK ;
Harris, A ;
Davis, CW ;
Randell, SH .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1999, 20 (04) :595-604
[6]   RAPID ANALYSIS OF AMINO-ACIDS USING PRE-COLUMN DERIVATIZATION [J].
BIDLINGMEYER, BA ;
COHEN, SA ;
TARVIN, TL .
JOURNAL OF CHROMATOGRAPHY, 1984, 336 (01) :93-104
[7]   Evidence for stem-cell niches in the tracheal epithelium [J].
Borthwick, DW ;
Shahbazian, M ;
Krantz, QT ;
Dorin, JR ;
Randell, SH .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2001, 24 (06) :662-670
[8]   RELATIVE EXPRESSION OF THE HUMAN EPITHELIAL NA+ CHANNEL SUBUNITS IN NORMAL AND CYSTIC-FIBROSIS AIRWAYS [J].
BURCH, LH ;
TALBOT, CR ;
KNOWLES, MR ;
CANESSA, CM ;
ROSSIER, BC ;
BOUCHER, RC .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1995, 269 (02) :C511-C518
[9]   Mucins (MUC1 and MUC3) of gastrointestinal and breast epithelia reveal different and heterogeneous tumor-associated aberrations in glycosylation [J].
Cao, Y ;
Blohm, D ;
Ghadimi, BM ;
Stosiek, P ;
Xing, PX ;
Karsten, U .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1997, 45 (11) :1547-1557
[10]   Genome-wide search and identification of a novel gel-forming mucin MUC19/Muc19 in glandular tissues [J].
Chen, Y ;
Zhao, YH ;
Kalaslavadi, TB ;
Halmati, E ;
Nehrke, K ;
Le, AD ;
Ann, DK ;
Wu, R .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2004, 30 (02) :155-165