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University of Wales College of Medicine, Department of Medical Biochemistry and
* Wales Heart Research Institute, Heath Park, Cardiff CF14 4XN, Wales, U.K.
1Correspondence: Bristol Heart Institute, Bristol Royal Infirmary, Level 7, Upper Maudlin St., Bristol BS2 8HW, England, U.K. E-mail: e.oviedo-orta{at}bristol.ac.uk
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-
-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., Gasque,
P., Evans, W. H. Immunoglobulin and cytokine expression in mixed
lymphocyte cultures is reduced by disruption of gap junction
intercellular communication.
Key Words: connexins intercellular communication interleukins mimetic peptides interferon gamma
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