Ecto-5'-nucleotidase (CD73) decreases mortality and organ injury in sepsis.
Ecto-5'-nucleotidase (CD73) decreases mortality and organ injury in sepsis.
复制标题
DOI：
10.4049/jimmunol.1003379
复制
发表时间：
2011-10-15
期刊：
影响因子：
--
通讯作者：
Németh ZH
中科院分区：
文献类型：
--
作者：
Haskó G;Csóka B;Koscsó B;Chandra R;Pacher P;Thompson LF;Deitch EA;Spolarics Z;Virág L;Gergely P;Rolandelli RH;Németh ZH
脓毒症时细胞外腺苷浓度升高，腺苷受体调节宿主对脓毒症的反应。在这里，我们研究了产生胞外酶的腺苷，胞外-5‘-核苷酸酶(CD73)在脓毒症中调节免疫和器官功能的作用。对CD73基因敲除(KO)和野生型(WT)小鼠进行盲肠结扎和穿孔，建立多菌败血症模型。与WT小鼠相比，CD73 KO小鼠的死亡率增加，这与细菌计数增加以及血液和腹膜中炎性细胞因子和趋化因子浓度升高有关。CD73缺乏可促进肺损伤，表现为髓过氧化物酶活性升高、中性粒细胞浸润和肺细胞因子水平升高。CD73KO小鼠胸腺细胞凋亡率增加，caspase3、多聚腺苷二磷酸核糖聚合酶和核因子κB活性增加，败血症CD73KO小鼠血尿素氮水平升高，肾脏细胞因子水平升高，提示肾功能障碍加重。CD73KO小鼠肾脏损伤加重与p38MAPK激活增强、Akt磷酸化降低有关。使用AMPCP在WT小鼠中的CD73药物灭活可增加血液和腹膜灌洗液中的细胞因子水平。这些发现表明CD73衍生的腺苷在脓毒症中可能是有益的。
The extracellular concentrations of adenosine are elevated during sepsis and adenosine receptors regulate the host’s response to sepsis. Here, we investigated the role of the adenosine generating ectoenzyme, ecto-5′-nucleotidase (CD73) in regulating immune and organ function during sepsis. Polymicrobial sepsis was induced by subjecting CD73 knockout (KO) and wild type (WT) mice to cecal ligation and puncture. CD73 KO mice showed increased mortality in comparison with WT mice, which was associated with increased bacterial counts and elevated inflammatory cytokine and chemokine concentrations in the blood and peritoneum. CD73 deficiency promoted lung injury as indicated by increased myeloperoxidase activity and neutrophil infiltration, and elevated pulmonary cytokine levels. CD73 KO mice had increased apoptosis in the thymus, as evidenced by increased activation of caspase-3, poly(ADP-ribose) polymerase and NF-κB. Septic CD73 KO mice had higher blood urea nitrogen levels and elevated cytokine levels in the kidney, indicating increased renal dysfunction. The increased kidney injury of CD73 KO mice was associated with augmented activation of p38 MAPK and decreased phosphorylation of Akt. Pharmacological inactivation of CD73 in WT mice using AMPCP augmented cytokine levels in the blood and peritoneal lavage fluid. These findings suggest that CD73-derived adenosine may be beneficial in sepsis.
登录
查看更多内容
影响因子：
15.9
作者：
Guo, RF;Huber-Lang, M;Ward, PA
通讯作者：
Ward, PA
影响因子：
20.3
作者：
Eltzschig, HK;Thompson, LF;Colgan, SP
通讯作者：
Colgan, SP
DOI：
10.1164/rccm.200109-014oc
发表时间：
2002-07-01
影响因子：
24.7
作者：
Cohen, ES;Law, WR;Hollenberg, SM
通讯作者：
Hollenberg, SM
影响因子：
3.7
作者：
Csóka B;Németh ZH;Mukhopadhyay P;Spolarics Z;Rajesh M;Federici S;Deitch EA;Bátkai S;Pacher P;Haskó G
通讯作者：
Haskó G
DOI：
10.4049/jimmunol.1000108
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ernst PB;Garrison JC;Thompson LF
通讯作者：
Thompson LF