Altered ion transport by tracheal glands in cystic fibrosis

M. Yamaya, W. E. Finkbeiner, Jonathan Widdicombe

Research output: Contribution to journalArticle

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 (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume261
Issue number6 5-3
StatePublished - 1991
Externally publishedYes

Fingerprint

Ion Transport
Cystic Fibrosis
Fibrosis
Methacholine Chloride
Bradykinin
Isoproterenol
Collagen
Fluids and Secretions
Mucus
Cyclic AMP
Digestion
Intercellular Signaling Peptides and Proteins

Keywords

  • Cell culture
  • Fluid movement
  • Ussing chambers

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

Altered ion transport by tracheal glands in cystic fibrosis. / Yamaya, M.; Finkbeiner, W. E.; Widdicombe, Jonathan.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 261, No. 6 5-3, 1991.

Research output: Contribution to journalArticle

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