Immunoglobulin and cytokine expression in mixed lymphocyte cultures is reduced by disruption of gap junction intercellular communication
Immunoglobulin and cytokine expression in mixed lymphocyte cultures is reduced by disruption of gap junction intercellular communication
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DOI：
10.1096/fj.00-0288com
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发表时间：
2001-03-01
期刊：
影响因子：
4.8
通讯作者：
Evans, WH
中科院分区：
文献类型：
--
作者：
Oviedo-Orta, E;Gasque, P;Evans, WH
缝隙连接蛋白(Cx)是组装成缝隙连接细胞间通讯通道的蛋白质亚基，在初级淋巴或器官和循环白细胞中表达，人扁桃体来源的T和B淋巴细胞表达Cx40和43，循环中的人T、B和NK淋巴细胞表达Cx43并直接相互转移一种低分子染料，表明存在功能性缝隙连接。我们现在确定了免疫系统中由缝隙连接所担保的特定特性。混合淋巴细胞在两种对缝隙连接通讯具有独立抑制作用的试剂--连接蛋白模拟肽和18-α-甘草次酸存在下，可显著减少IgM、IGC和IgA的分泌。这两类缝隙连接抑制剂也降低了纯化B细胞分泌这些免疫球蛋白的能力。此外，还观察到了对IL-10基因表达的复杂的时间抑制效应，结果表明，细胞间的缝隙连接信号是免疫系统代谢协作机制的重要组成部分。
Connexins (Cx), the protein subunits assembled into gap junction intercellular communication channels, are expressed in primary lymphoid or 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, Igc, 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.