Altered ion transport by tracheal glands in cystic fibrosis

M. Yamaya, W. E. Finkbeiner, J. H. Widdicombe

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44 Citations (Scopus)

Abstract

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 cells sheets formed after 20 days. Cells were then isolated by trypsinization and replated at 106 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 (R(te)) and baseline short-circuit current (I(sc)) of CF cultures (171 ± 67 Ω·cm2, 3.8 ± 0.8 μA/cm2; n = 5 were significantly less than non-CF (541 ± 116 Ω·cm2, 9.9 ± 2.3 μA/cm2, n = 14). Responses in I(sc) 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 μA/cm2; n = 5 for CF, n = 14 for non-CF. When CF and non-CF cells were matched for baseline I(sc) and R(te), 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.

Original languageEnglish
Pages (from-to)L491-L494
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume261
Issue number6 5-3
DOIs
Publication statusPublished - 1991

Keywords

  • Cell culture
  • Fluid movement
  • Ussing chambers

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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