Harmful Roles of TLR3 and TLR9 in Cardiac Dysfunction Developing during Polymicrobial Sepsis.
Harmful Roles of TLR3 and TLR9 in Cardiac Dysfunction Developing during Polymicrobial Sepsis.
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DOI：
10.1155/2018/4302726
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发表时间：
2018
影响因子：
--
通讯作者：
Ward PA
中科院分区：
文献类型：
--
作者：
Fattahi F;Russell MW;Malan EA;Parlett M;Abe E;Zetoune FS;Ward PA
我们确定了TLR 3和TLR 9在多微生物败血症不良事件中的作用，重点是脓毒性心肌病的发展，我们最近发现其进展是补体和组蛋白依赖性的。所以Wt，TLR 3敲除（K.O.），和TLR 9-K.O.小鼠在盲肠结扎和穿孔（CLP）后经受多微生物脓毒症。在缺乏TLR 3或TLR 9的情况下，在心肌病发展过程中超声心动图（Echo）-多普勒功能障碍的强度在K.O.小鼠基于我们先前强调血浆C5 a和组蛋白在脓毒症心肌病中的不良作用的研究，在TLR 3-和TLR 9-K.O.在小鼠中，CLP后血浆和心脏组织中C5 a和组蛋白的血浆水平以及细胞因子的水平显著降低。由于我们知道组蛋白会导致心功能不全，因此将大鼠心肌细胞（CM）暴露于组蛋白（从小牛胸腺中纯化），这导致CM表面形成水泡，表明组蛋白可能会扰乱CM的细胞膜。在体外，CM暴露于组蛋白3小时引起CM释放乳酸脱氢酶。这些数据表明脓毒症诱导的心功能不全需要TLR 3和TLR 9的存在，并且可能与组蛋白诱导的CM损伤有关。
We determined the roles of TLR3 and TLR9 in adverse events of polymicrobial sepsis, with a focus on development of septic cardiomyopathy, progression of which we have recently shown to be complement- and histones-dependent. So Wt, TLR3-knocked out (K.O.), and TLR9-K.O. mice were subjected to polymicrobial sepsis following cecal ligation and puncture (CLP). In the absence of either TLR3 or TLR9, the intensity of echocardiogram (Echo)-Doppler dysfunction during development of cardiomyopathy was substantially reduced in the K.O. mice. Based on our prior studies emphasizing the adverse effects of plasma C5a and histones in the cardiomyopathy of sepsis, in TLR3- and TLR9-K.O. mice, there were striking reductions in plasma levels of C5a and histones as well as reduced levels of cytokines in plasma and heart tissue after CLP. Since we know that histones cause cardiac dysfunction, rat cardiomyocytes (CMs) were exposed in vitro to the histones (purified from calf thymus), which caused bleb formation on the surfaces of CMs, suggesting histones may perturb the cell membrane of CMs. In vitro, exposure of CMs to the histones for 3 hours caused lactate dehydrogenase release from CMs. These data indicate that sepsis-induced cardiac dysfunction requires presence of TLR3 and TLR9 and may be linked to histone-induced damage of CMs.
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影响因子：
4.4
作者：
Fattahi, Fatemeh;Grailer, Jamison J.;Jajou, Lawrence;Zetoune, Firas S.;Andjelkovic, Anuska V.;Ward, Peter A.
通讯作者：
Ward, Peter A.
影响因子：
20.1
作者：
Ackers-Johnson M;Li PY;Holmes AP;O'Brien SM;Pavlovic D;Foo RS
通讯作者：
Foo RS
DOI：
10.1152/ajpheart.00398.2006
发表时间：
2007-01-01
影响因子：
4.8
作者：
Hardarson, Hordur S.;Baker, J. Scott;Vallejo, Jesus G.
通讯作者：
Vallejo, Jesus G.
影响因子：
8.8
作者：
Alves, JC;de Freitas, A;Cunha, FQ
通讯作者：
Cunha, FQ
影响因子：
4.6
作者：
Boehm O;Markowski P;van der Giet M;Gielen V;Kokalova A;Brill C;Hoeft A;Baumgarten G;Meyer R;Knuefermann P
通讯作者：
Knuefermann P