Adenosine signaling via the adenosine 2B receptor is involved in bronchiolitis obliterans development.
Adenosine signaling via the adenosine 2B receptor is involved in bronchiolitis obliterans development.
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通过腺苷2B受体通过腺苷信号传导参与闭塞性的支气管炎。
DOI：
10.1016/j.healun.2010.07.005
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Lau CL
中科院分区：
文献类型：
--
作者：
Zhao Y;LaPar DJ;Steidle J;Emaminia A;Kron IL;Ailawadi G;Linden J;Lau CL
腺苷是响应于缺血或炎症而产生的，并保护组织免受损伤。存在四种腺苷受体，其在限制和终止组织特异性和全身性炎症反应的生理负反馈机制中起关键作用。越来越多的证据集中在腺苷2A受体（A2 AR）的抗炎和免疫抑制作用，我们以前曾报道过它在肺移植后闭塞性细支气管炎（BO）的发展中的作用。然而，很少有研究报道腺苷2B受体（A2 BR）在BO中的作用。数据表明，A2 BR具有促炎和促纤维化作用。我们假设通过A2 BR的腺苷信号传导参与BO的发展。使用完全同种异体抗原错配的鼠异位气管模型研究BO中的A2 BR信号传导。气管移植物由移植到野生型或A2 BR敲除C57 BL/6受体中的Balb/c供体气管组成。移植后3、7、12和21天取出移植的气管。苏木精-伊红染色观察管腔闭塞情况，免疫组化染色观察细胞浸润情况（巨噬细胞、中性粒细胞、CD 3+和Foxp 3+调节性T细胞）。与野生型受体中的同种异体移植物相比，移植到A2 BR敲除小鼠中的气管在第21天显示出较少的BO发展。在第7天，与野生型相比，A2 BR敲除小鼠的CD 3 + T细胞和CD 4 +/CD 25 +/Foxp 3+调节性T细胞增加。到第12天，与A2 BR KO小鼠相比，野生型气管中存在更多的CD 3 + T细胞，但A2 BR KO小鼠气管中CD 4 +/CD 25 +/Foxp 3+调节性T细胞的百分比仍然较高。A2 BR刺激可能通过抑制CD 4 +/CD 25 +/Foxp 3+调节性T细胞浸润而促进BO的发生发展。
Adenosine is produced in response to ischemia or inflammation and protects tissues from injury. There are four adenosine receptors, which play a critical role in the physiological negative-feedback mechanism for limitation and termination of tissue-specific and systemic inflammatory responses. Accumulating evidence has focused on the anti-inflammatory and immunosuppressive role of the adenosine 2A receptor (A2AR), and we have previously reported on its’ role in the development of bronchiolitis obliterans (BO) following lung transplantation. However, few studies have reported on the role of the adenosine 2B receptor (A2BR) in BO. Data suggests that the A2BR has pro-inflammatory and profibrotic roles. We hypothesized that adenosine signaling through the A2BR is involved in the development of BO. A murine heterotopic tracheal model across a total alloantigeneic mismatch was used to study A2BR signaling in BO. Tracheal transplants consisted of Balb/c donor tracheas transplanted into wild-type or A2BR knockout C57BL/6 recipients. Transplanted tracheas were removed 3, 7, 12, and 21 days after transplantation. The luminal obliteration was evaluated through hematoxylin and eosin staining and the cellular infiltration (macrophage, neutrophil, CD3+ and Foxp3+ regulatory T cell) was detected by immunohistochemical staining. In comparison to allografts in wild type recipients, tracheas transplanted into A2BR knockout mice displayed less BO development on day 21. A2BR knockout mice had an increase in CD3+ T cells and CD4+/CD25+/Foxp3+ regulatory T cells when compared to wild type on day 7. By day 12, more CD3+ T cells were present in the wild-type trachea compared to the A2BR KO, but the percentage of CD4+/CD25+/Foxp3+ regulatory T cells remained higher in the tracheas of A2BR KO mice. A2BR stimulation may promote the development of BO via inhibiting CD4+/CD25+/Foxp3+ regulatory T cell infiltration.
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DOI：
10.1084/jem.20061097
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lappas CM;Day YJ;Marshall MA;Engelhard VH;Linden J
通讯作者：
Linden J
DOI：
10.1016/j.jtcvs.2007.08.041
发表时间：
2008-01-01
影响因子：
6
作者：
Gazoni, Leo M.;Laubach, Victor E.;Kron, Irving L.
通讯作者：
Kron, Irving L.
影响因子：
4.6
作者：
Fiser, SM;Tribble, CG;Kron, IL
通讯作者：
Kron, IL
DOI：
10.1165/rcmb.2007-0450oc
发表时间：
2008-08-01
影响因子：
6.4
作者：
Rollins, Brett M.;Burn, Mellisa;Tarran, Robert
通讯作者：
Tarran, Robert
影响因子：
56.9
作者：
Hori, S;Nomura, T;Sakaguchi, S
通讯作者：
Sakaguchi, S