Immunoglobulin and cytokine expression in mixed lymphocyte cultures is reduced by disruption of gap junction intercellular communication.
Connexins (Cx), the protein subunits assembled into gap junction intercellular communication channels, are expressed in primary lymphoid organs and by circulating leukocytes. Human tonsil-derived T and B lymphocytes express Cx40 and 43; circulating human T, B, and NK lymphocytes express Cx43 and directly transfer between each other a low molecular dye indicative that functional gap junctions exist. We now identify specific properties in the immune system underwritten by gap junctions. Mixed lymphocytes cultured in the presence of two reagents with independent inhibitory action on gap junction communication, a connexin mimetic peptide and 18-alpha-glycyrrhetinic acid, markedly reduced the secretion of IgM, IgG, and IgA. The secretion of these immunoglobulins by purified B cells was also reduced by the two classes of gap junction inhibitors. Complex temporal inhibitory effects on the expression of mRNA encoding interleukins, especially IL-10, were also observed. The results indicate that intercellular signaling across gap junctions is an important component of the mechanisms underlying metabolic cooperation in the immune system.
Oviedo-Orta
E
E
University of Wales College of Medicine, Department of Medical Biochemistry, Wales Heart Research Institute, Heath Park, Cardiff CF14 4XN, Wales, U.K. e.oviedo-orta@bristol.ac.uk
Gasque
P
P
Evans
W H
WH
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D002648:Child; D017630:Connexins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D017629:Gap Junctions / Q000502:physiology*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology
D017630:Connexins; D016207:Cytokines; D007136:Immunoglobulins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D010455:Peptides; D010835:Phytohemagglutinins; C100156:leukoagglutinins, plants; D016753:Interleukin-10; D007371:Interferon-gamma; D006034:Glycyrrhetinic Acid