CD14-deficient mice are protected against lipopolysaccharide-induced cardiac inflammation and left ventricular dysfunction
CD14-deficient mice are protected against lipopolysaccharide-induced cardiac inflammation and left ventricular dysfunction
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DOI：
10.1161/01.cir.0000038110.69369.4c
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发表时间：
2002-11-12
期刊：
影响因子：
37.8
通讯作者：
Vallejo, JG
中科院分区：
文献类型：
--
作者：
Knuefermann, P;Nemoto, S;Vallejo, JG
脓毒症引起心肌功能障碍的分子机制尚不清楚。CD 14介导包括心脏在内的各种器官中对脂多糖（LPS）的炎症反应。在这项研究中，我们研究了CD 14在LPS诱导的心肌功能障碍中的作用invivo.Methods和Results-Wild-type和CD 14-deficient（CD 14-D）小鼠与大肠杆菌LPS的挑战。在LPS刺激前和6小时后测定心肌肿瘤坏死因子、白细胞介素-1 β（IL-1 β）和NOS 2诱导。在注射LPS前和注射LPS后6小时分别测定超声心动图左室功能参数。LPS攻击诱导野生型小鼠心肌肿瘤坏死因子和IL-1 β mRNA和蛋白表达显著增加。相反，TNF和IL-1 β的mRNA和蛋白水平在CD 14-D小鼠中显著减弱。仅在野生型小鼠的心脏中，在LPS激发的6小时内注意到NOS 2蛋白的增加。这与心室cGMP水平的增加有关。在野生型小鼠的心脏中，在LPS的30分钟内观察到核因子-kappaB的活化，但在CD 14-D小鼠中没有。在野生型小鼠中，LPS显著降低左心室短轴缩短率、周向缩短速度和dP/dt（max）。LPS处理的CD 14-D小鼠保持正常的心脏功能。结论-这些结果表明，CD 14是重要的介导的促炎反应诱导的LPS在心脏和CD 14是必要的左心室功能障碍的发展过程中LPS诱导的休克在体内。
Background-The molecular mechanisms responsible for sepsis-induced myocardial dysfunction remain undefined. CD 14 mediates the inflammatory response to lipopolysaccharide (LPS) in various organs including the heart. In this study we investigated the role of CD14 in LPS-induced myocardial dysfunction in vivo.Methods and Results-Wild-type and CD14-deficient (CD14-D) mice were challenged with Escherichia coli LPS. Myocardial tumor necrosis factor, interleukin-1beta (IL-1beta), and NOS2 induction was measured before and 6 hours after LPS challenge. Echocardiographic parameters of left ventricular function were measured before and 6 hours after LPS administration. LPS challenge induced a significant increase in myocardial tumor necrosis factor and IL-1beta mRNA and protein expression in wild-type mice. In contrast, mRNA and protein levels for TNF and IL-1beta were significantly blunted in CD14-D mice. An increase in NOS2 protein was noted within 6 hours of LPS provocation only in the hearts of wild-type mice. This was associated with an increase in ventricular cGMP levels. Activation of nuclear factor-kappaB was observed within 30 minutes of LPS in the hearts of wild-type mice but not in CD14-D mice. In wild-type mice, LPS significantly decreased left ventricular fractional shortening, velocity of circumferential shortening, and dP/dt(max). LPS-treated CD14-D mice maintained normal cardiac function.Conclusions-These results suggest that CD14 is important in mediating the proinflammatory response induced by LPS in the heart and that CD 14 is necessary for the development of left ventricular dysfunction during LPS-induced shock in vivo.