AJP - Lung Cellular and Molecular Physiology, Vol 261, Issue 6 491-L494, Copyright © 1991 by American Physiological Society

ARTICLES

Altered ion transport by tracheal glands in cystic fibrosis

M. Yamaya, W. E. Finkbeiner and J. H. Widdicombe
Cystic Fibrosis Research Center, University of California, San Francisco 94143.

Acini of tracheal glands from 12 humans without cystic fibrosis (CF) and from two CF patients were isolated by enzymatic digestion. They were plated on flasks coated with human placental collagen (HPC) in media containing Ultroser G serum substitute and a variety of growth factors. Confluent cell sheets formed after 20 days. Cells were then isolated by trypsinization and replated at 10(6) cells/cm2 onto porous-bottomed inserts coated with HPC. Confluent sheets formed on day 1 after replating and were studied on day 10 in Ussing chambers. Transepithelial resistance (Rte) and baseline short-circuit current (Isc) of CF cultures (171 +/- 67 omega.cm2, 3.8 +/- 0.8 microA/cm2; n = 5) were significantly less than non-CF (541 +/- 116 omega.cm2, 9.9 +/- 2.3 microA/cm2; n = 14). Responses in Isc to mediators were also significantly reduced in CF: isoproterenol (10(-5)M) = 0.04 +/- 0.04 vs. 1.9 +/- 0.6; methacholine (10(-5)M) = 0.2 +/- 0.1 vs. 7.1 +/- 1.7; bradykinin (10(-6)M) = 0.4 +/- 0.1 vs. 5.0 +/- 1.0 microA/cm2; n = 5 for CF, n = 14 for non-CF. When CF and non-CF cells were matched for baseline Isc and Rte, the responses of CF cells to mediators still remained statistically lower than normal. The reduced responses of CF cells to bradykinin and methacholine, in addition to isoproterenol, suggest that both Ca-dependent and adenosine 3',5'-cyclic monophosphate-dependent regulation of Cl secretion are defective in CF tracheobronchial glands. The resulting reduction in fluid secretion by glands may contribute to the accumulation of airway mucus in CF.

This article has been cited by other articles:

				J. J. Wine Acid in the airways. Focus on "Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis" Am J Physiol Cell Physiol, March 1, 2006; 290(3): C669 - C671. [Full Text] [PDF]

				T. Irokawa, M. E. Krouse, N. S. Joo, J. V. Wu, and J. J. Wine A "virtual gland" method for quantifying epithelial fluid secretion Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L784 - L793. [Abstract] [Full Text] [PDF]

				A. S. Verkman, Y. Song, and J. R. Thiagarajah Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease Am J Physiol Cell Physiol, January 1, 2003; 284(1): C2 - C15. [Abstract] [Full Text] [PDF]

				N. S. Joo, T. Irokawa, J. V. Wu, R. C. Robbins, R. I. Whyte, and J. J. Wine Absent Secretion to Vasoactive Intestinal Peptide in Cystic Fibrosis Airway Glands J. Biol. Chem., December 20, 2002; 277(52): 50710 - 50715. [Abstract] [Full Text] [PDF]

				N. S. Joo, Y. Saenz, M. E. Krouse, and J. J. Wine Mucus Secretion from Single Submucosal Glands of Pig. STIMULATION BY CARBACHOL AND VASOACTIVE INTESTINAL PEPTIDE J. Biol. Chem., July 26, 2002; 277(31): 28167 - 28175. [Abstract] [Full Text] [PDF]

				K. Kunzelmann and M. Mall Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease Physiol Rev, January 1, 2002; 82(1): 245 - 289. [Abstract] [Full Text] [PDF]

				N. S. Joo, J. V. Wu, M. E. Krouse, Y. Saenz, and J. J. Wine Optical method for quantifying rates of mucus secretion from single submucosal glands Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L458 - L468. [Abstract] [Full Text] [PDF]

				J. Loffing, B. D. Moyer, D. Reynolds, B. E. Shmukler, S. L. Alper, and B. A. Stanton Functional and molecular characterization of an anion exchanger in airway serous epithelial cells Am J Physiol Cell Physiol, October 1, 2000; 279(4): C1016 - C1023. [Abstract] [Full Text] [PDF]

				J.-C. Allo, P. Midoux, M. Merten, E. Souil, J. Lipecka, C. Figarella, M. Monsigny, P. Briand, and I. Fajac Efficient Gene Transfer into Human Normal and Cystic Fibrosis Tracheal Gland Serous Cells with Synthetic Vectors Am. J. Respir. Cell Mol. Biol., February 1, 2000; 22(2): 166 - 175. [Abstract] [Full Text]

				C. Jiang, W. E. Finkbeiner, J. H. Widdicombe, S. L. Fang, K. X. Wang, J. B. Nietupski, K. M. Hehir, and S. H. Cheng Restoration of Cyclic Adenosine Monophosphate-Stimulated Chloride Channel Activity in Human Cystic Fibrosis Tracheobronchial Submucosal Gland Cells by Adenovirus-Mediated and Cationic Lipid-Mediated Gene Transfer Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1107 - 1115. [Abstract] [Full Text]

				D. C. Devor and J. M. Pilewski UTP inhibits Na+ absorption in wild-type and Delta F508 CFTR-expressing human bronchial epithelia Am J Physiol Cell Physiol, April 1, 1999; 276(4): C827 - C837. [Abstract] [Full Text] [PDF]

				J. M. PILEWSKI and R. A. FRIZZELL Role of CFTR in Airway Disease Physiol Rev, January 1, 1999; 79(1): 215 - 255. [Abstract] [Full Text] [PDF]

				D. Duan, A. Sehgal, J. Yao, and J. F. Engelhardt Lef1 Transcription Factor Expression Defines Airway Progenitor Cell Targets for In Utero Gene Therapy of Submucosal Gland in Cystic Fibrosis Am. J. Respir. Cell Mol. Biol., June 1, 1998; 18(6): 750 - 758. [Abstract] [Full Text]

				L. Trout, M. King, W. Feng, S. K. Inglis, and S. T. Ballard Inhibition of airway liquid secretion and its effect on the physical properties of airway mucus Am J Physiol Lung Cell Mol Physiol, February 1, 1998; 274(2): L258 - L263. [Abstract] [Full Text] [PDF]

				S. Moon, M. Singh, M. E. Krouse, and J. J. Wine Calcium-stimulated Cl- secretion in Calu-3 human airway cells requires CFTR Am J Physiol Lung Cell Mol Physiol, December 1, 1997; 273(6): L1208 - L1219. [Abstract] [Full Text] [PDF]

				S. Jayaraman, N. S. Joo, B. Reitz, J. J. Wine, and A. S. Verkman Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na+] and pH but elevated viscosity PNAS, July 3, 2001; 98(14): 8119 - 8123. [Abstract] [Full Text] [PDF]