Adenosine A2A receptor activation on CD4+ T lymphocytes and neutrophils attenuates lung ischemia-reperfusion injury.
Adenosine A2A receptor activation on CD4+ T lymphocytes and neutrophils attenuates lung ischemia-reperfusion injury.
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DOI：
10.1016/j.jtcvs.2009.08.033
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发表时间：
2010-02
影响因子：
6
通讯作者：
Yang, Zequan
中科院分区：
文献类型：
--
作者：
Sharma, Ashish K.;Laubach, Victor E.;Ramos, Susan I.;Zhao, Yunge;Stukenborg, George;Linden, Joel;Kron, Irving L.;Yang, Zequan
腺苷A2 A受体激活可有效减轻肺缺血再灌注损伤本研究验证了腺苷A2 A受体激活通过抑制CD 4 + T细胞激活和随后的中性粒细胞浸润来减轻缺血再灌注损伤的假设。采用肺缺血再灌注损伤的体内模型。将C57 BL/6小鼠分配到假手术组（左胸廓切开术）或经历缺血-再灌注（左肺门闭塞1小时加再灌注2小时）的七个研究组。在再灌注前5分钟给予ATL 313，一种选择性腺苷A2 A受体激动剂，有或没有中性粒细胞或CD 4 + T细胞的抗体耗竭。再灌注后，测量以下内容：使用分离的缓冲液灌注肺系统的肺功能，通过免疫组织化学的T细胞浸润，支气管肺泡灌洗液中的髓过氧化物酶和促炎细胞因子/趋化因子水平，肺湿/干重和微血管通透性。与对照组相比，ATL 313显著改善了肺功能，并减少了缺血-再灌注后的水肿和微血管通透性。免疫组织化学和髓过氧化物酶含量显示，在ATL 313处理的小鼠中，缺血再灌注后中性粒细胞和CD 4 + T细胞的浸润显著减少。尽管CD 4 + T细胞耗尽和嗜中性粒细胞耗尽的小鼠显示出显著降低的肺损伤，但当向这些小鼠施用ATL 313时，没有发生额外的保护。TNF-α、IL-17、KC、MCP-1、MIP-1和RANTES的表达在中性粒细胞和CD 4 + T细胞耗竭的小鼠中显著降低，并且仅在嗜中性粒细胞耗竭的小鼠中被ATL 313进一步降低。这些结果表明，CD 4 + T细胞在介导缺血-再灌注后的肺部炎症中起关键作用。ATL 313可能主要通过激活CD 4 + T细胞和中性粒细胞上的腺苷A2 A受体来发挥其保护作用。
Adenosine A2A receptor activation potently attenuates lung ischemia-reperfusion injury. This study tests the hypothesis that adenosine A2A receptor activation attenuates ischemia-reperfusion injury by inhibiting CD4+ T cell activation and subsequent neutrophil infiltration. An in vivo model of lung ischemia-reperfusion injury was used. C57BL/6 mice were assigned to either sham group (left thoracotomy) or seven study groups which underwent ischemia-reperfusion (1hr left hilar occlusion plus 2hrs reperfusion). ATL313, a selective adenosine A2A receptor agonist, was administered five minutes before reperfusion with or without antibody depletion of neutrophils or CD4+ T cells. After reperfusion, the following was measured: pulmonary function using an isolated, buffer-perfused lung system, T cell infiltration by immunohistochemistry, myeloperoxidase and proinflammatory cytokine/chemokine levels in bronchoalveolar lavage fluid, lung wet/dry weight, and microvascular permeability. ATL313 significantly improved pulmonary function and reduced edema and microvascular permeability after ischemia-reperfusion compared to control. Immunohistochemistry and myeloperoxidase content demonstrated significantly reduced infiltration of neutrophils and CD4+ T cells after ischemia-reperfusion in ATL313-treated mice. Although CD4+ T cell-depleted and neutrophil-depleted mice displayed significantly reduced lung injury, no additional protection occurred when ATL313 was administered to these mice. Expression of TNF-α, IL-17, KC, MCP-1, MIP-1, and RANTES were significantly reduced in neutrophil- and CD4+ T cell-depleted mice and reduced further by ATL313 only in neutrophil-depleted mice. These results demonstrate that CD4+ T cells play a key role in mediating lung inflammation after ischemia-reperfusion. ATL313 likely exerts its protective effect largely through activation of adenosine A2A receptors on CD4+ T cells and neutrophils.
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影响因子：
4.4
作者：
Reutershan, Jorg;Cagnina, Rebecca E.;Ley, Klaus
通讯作者：
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DOI：
10.1016/j.jtcvs.2007.08.041
发表时间：
2008-01-01
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10.1152/ajplung.00086.2006
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2006-11-01
影响因子：
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