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

• Published in: Pflügers Archiv 2001-01, Vol.443 Suppl 1, p.S36-S39
• Main Author: Bubien, J K
• Format: Article
• Language: English
• Subjects: Cells, Cultured; Cyclic AMP - analogs & derivatives; Cyclic AMP - pharmacology; Cystic fibrosis; Cystic Fibrosis - immunology; Cystic Fibrosis - metabolism; Cystic Fibrosis - physiopathology; Cystic Fibrosis Transmembrane Conductance Regulator - secretion; Enzyme Inhibitors - pharmacology; Epithelial Sodium Channels; Humans; Immunoglobulin Light Chains - metabolism; Lung - metabolism; Lung - physiopathology; Lymphocytes; Lymphocytes - cytology; Lymphocytes - secretion; Patch-Clamp Techniques; Pneumonia - immunology; Pneumonia - metabolism; Signal transduction; Sodium Channels - metabolism; Thionucleotides - pharmacology
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s004240100641

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).