Regulation of leukocyte function by adenosine receptors.
Regulation of leukocyte function by adenosine receptors.
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DOI：
10.1016/b978-0-12-385526-8.00004-7
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Linden, Joel
中科院分区：
文献类型：
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作者：
Linden, Joel
免疫系统对微环境中的提示做出反应，以做出急性和慢性适应，以应对炎症和损伤。本地产生的嘌呤核苷酸和腺苷为免疫系统的所有骨髓来源细胞提供受体介导的信号，以调节它们的反应。本文综述了腺苷通过G蛋白偶联的腺苷受体对免疫系统细胞的影响的最新研究进展。腺苷A2a受体(A2ARs)对免疫细胞的激活具有普遍的抑制作用。此外，它们的转录受到信号的强烈诱导，这些信号通过Toll样受体激活巨噬细胞或树突状细胞，或者通过T细胞受体激活T细胞。A2AR的诱导负责产生炎症反应的逐渐消散。A2AR激活在限制在急性再灌注损伤中起核心作用的不变NKT(INKT)细胞的激活方面尤其有效。A2a激动剂在治疗血管闭塞组织损伤方面具有临床应用前景。阻断A2a受体可能有助于增强免疫介导的对癌细胞的杀伤。A2BR的表达也受低氧、细胞因子和氧自由基的转录调控。A2BR的急性激活减少了巨噬细胞产生的致炎细胞因子，但持续的激活促进了巨噬细胞和树突状细胞的重塑以及急性期蛋白和血管生成因子的产生，这些可能参与了胰岛素抵抗和组织纤维化的发生。A2BR的激活还通过影响抗炎网织蛋白受体Unc5b的表达来影响巨噬细胞和中性粒细胞的功能。对腺苷介导的免疫系统作用的治疗意义进行了讨论。
The immune system responds to cues in the microenvironment to make acute and chronic adaptations in response to inflammation and injury. Locally produced purine nucleotides and adenosine provide receptor-mediated signaling to all bone-marrow derived cells of the immune system to modulate their responses. This review summarizes recent advances in our understanding of the effects of adenosine signaling through G protein-coupled adenosine receptors on cells of the immune system. Adenosine A2A receptors (A2ARs) have a generally suppressive effect on the activation of immune cells. Moreover, their transcription is strongly induced by signals that activate macrophages or dendritic cells through toll-like receptors, or T cells through T cell receptors. A2AR induction is responsible for producing a gradual dissipation of inflammatory responses. A2AR activation is particularly effective in limiting the activation of invariant NKT (iNKT) cells that play a central role in acute reperfusion injury. A2A agonists have clinical promise for the treatment of vaso-occlusive tissue injury. Blockade of A2A receptors may be useful to enhance immune-mediated killing of cancer cells. A2BR expression also is transcriptionally regulated by hypoxia, cytokines, and oxygen radicals. Acute A2BR activation attenuates the production of proinflammatory cytokines from macrophages, but sustained activation facilitates macrophage and dendritic cell remodeling and the production of acute phase proteins and angiogenic factors that may participate in evoking insulin resistance and tissue fibrosis. A2BR activation also influences macrophage and neutrophil function by influencing expression of the anti-inflammatory netrin receptor, UNC5B. The therapeutic significance of adenosine-mediated effects on the immune system is discussed.