CFTR may play a role in regulated secretion by lymphocytes: a new hypothesis for the pathophysiology of cystic fibrosis

Pflugers Arch. 2001:443 Suppl 1:S36-9. doi: 10.1007/s004240100641. Epub 2001 Jul 7.

Abstract

Human lymphocytes and pancreatic acinar cells have a common function: both cell types secrete specific proteins in response to extracellular signals. Acinar cells secrete digestive enzymes, while lymphocytes secrete antibodies and cytokines. Both cell types utilize similar receptor-mediated activation systems, similar signal transduction pathways (i.e., alpha adrenergic receptors, and cAMP), and express the cystic fibrosis transmembrane conductance regulator (CFTR). Preliminary tests of the hypothesis that B lymphocytes are capable of regulated secretion were carried out using transformed lymphocytes. lambda light chain secretion rates were measured in response to treatment with 8-CPT-cAMP. A rapid transient increase in secretion was observed in non-CF lymphocytes. This effect was absent in CF lymphocytes. A failure of regulated secretion could cause a reduced response to antigen presentation, and an inability to completely clear pathogens such as Pseudomonas aeruginosa. Another piece of circumstantial evidence is that lung-transplanted CF patients remain chronically ill. While immunosuppressive therapy may contribute to the chronic illness, the phenomenon is more acute in CF lung-transplant patients than non-CF lung-transplant recipients receiving the same immunosuppressive therapy. A defect in regulated secretion of antibodies and cytokines in response to antigens may be the source of a long suspected, but as yet unproved CFTR-mediated immunological defect underlying the pulmonary morbidity and mortality in cystic fibrosis (CF).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Cyclic AMP / analogs & derivatives*
  • Cyclic AMP / pharmacology
  • Cystic Fibrosis / immunology
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / physiopathology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Epithelial Sodium Channels
  • Humans
  • Immunoglobulin Light Chains / metabolism
  • Lung / metabolism
  • Lung / physiopathology
  • Lymphocytes / cytology
  • Lymphocytes / metabolism*
  • Patch-Clamp Techniques
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Sodium Channels / metabolism
  • Thionucleotides / pharmacology

Substances

  • CFTR protein, human
  • Enzyme Inhibitors
  • Epithelial Sodium Channels
  • Immunoglobulin Light Chains
  • Sodium Channels
  • Thionucleotides
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
  • Cyclic AMP