title: CFTR may play a role in regulated secretion by lymphocytes: a new hypothesis for the pathophysiology of cystic fibrosis.
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).
authors.affiliation: Department of Physiology and Biophysics, 726 MCLM, University of Alabama at Birmingham, Birmingham, AL 35214, USA. bubien@uab.edu
authors.forename: J K
authors.initials: JK
authors.lastname: Bubien
mesh_terms: D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: C505032:CFTR protein, human; D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D007147:Immunoglobulin Light Chains; D015222:Sodium Channels; D013873:Thionucleotides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP