Regulation of lymphocyte function by adenosine.
Regulation of lymphocyte function by adenosine.
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DOI：
10.1161/atvbaha.111.226837
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发表时间：
2012-09
期刊：
影响因子：
--
通讯作者：
Cekic C
中科院分区：
文献类型：
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作者：
Linden J;Cekic C
腺苷调节淋巴细胞和脉管系统之间的相互作用，并且对于控制响应于组织损伤或感染的淋巴细胞运输是重要的。腺苷可主要通过激活腺苷A2 A受体（A2 AR）和经由环AMP和蛋白激酶A（PKA）的信号传导来减弱T细胞受体（TCR）激活的作用。PKA通过C-末端Src激酶（Csk）、活化T细胞核因子（NF-AT）和环AMP反应元件结合蛋白（CREB）的磷酸化来减少近端TCR信号传导。PKA活化可以增强或抑制T细胞的存活，这取决于信号传导的强度和持续时间。诱导酶如CD 73和CD 39调节腺苷在体内的形成和降解。淋巴细胞通过血管的外渗受到A2 AR介导的对淋巴细胞上细胞间粘附分子1（ICAM）表达的抑制以及对活化的淋巴细胞具有趋化性的IFNγ和IFNγ诱导型趋化因子的产生减少的影响。腺苷还通过激活A2 BR降低血管内皮的屏障功能。总之，腺苷信号传导通过受体和酶的诱导受到组织炎症和损伤的影响，并且由于PKA介导的对粘附分子、IFNγ产生和内皮屏障功能的作用，腺苷信号传导通常对淋巴细胞迁移到炎症组织中具有抑制作用。
Adenosine regulates the interaction between lymphocytes and the vasculature and is important for controlling lymphocyte trafficking in response to tissue injury or infection. Adenosine can blunt the effects of T cell receptor (TCR) activation primarily by activating adenosine A2A receptors (A2AR) and signaling via cyclic AMP and protein kinase A (PKA). PKA reduces proximal TCR signaling by phosphorylation of C-terminal Src kinase (Csk), nuclear factor of activated T cells (NF-AT) and cyclic AMP response element binding protein (CREB). PKA activation can either enhance or inhibit the survival of T cells depending on the strength and duration of signaling. Inducible enzymes such as CD73 and CD39 regulate adenosine formation and degradation in vivo. The extravasation of lymphocytes through blood vessels is influenced by A2AR-mediated suppression of Intercellular Adhesion Molecule 1 (ICAM) expression on lymphocytes and diminished production of IFNγ and IFNγ-inducible chemokines that are chemotactic to activated lymphocytes. Adenosine also decreases the barrier function of vascular endothelium by activating A2BRs. In sum, adenosine signaling is influenced by tissue inflammation and injury through induction of receptors and enzymes and has generally inhibitory effects on lymphocyte migration into inflamed tissues due to PKA-mediated effects on adhesion molecules, IFNγ production and endothelial barrier function.