THE OUTCOME OF POLYMICROBIAL SEPSIS IS INDEPENDENT OF T AND B CELLS
THE OUTCOME OF POLYMICROBIAL SEPSIS IS INDEPENDENT OF T AND B CELLS
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DOI：
10.1097/shk.0b013e3182295f5f
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发表时间：
2011-10-01
期刊：
影响因子：
3.1
通讯作者：
Ward, Peter A.
中科院分区：
文献类型：
--
作者：
Bosmann, Markus;Russkamp, Norman F.;Ward, Peter A.
获得性免疫系统和先天性免疫系统对脓毒症发病机制和转归的作用仍然是一个基本而有争议的问题。在这里，我们使用缺乏重组激活基因1（Rag-1）的小鼠来研究盲肠结扎穿孔（CLP）后脓毒症中T和B细胞的作用。Rag-1（-/-）小鼠脾脏萎缩，完全缺乏CD 3（+）T细胞和CD 19（+）B细胞。野生型小鼠和Rag-1（-/-）小鼠（均为C57 BL/6 J背景）接受CLP或假手术。野生型和Rag-1（-/-）小鼠在CLP后第一天内均出现脓毒症的临床体征。这包括通过体表温度降低测量的重度体温过低和通过血尿素氮和乳酸脱氢酶水平的血浆升高检测的器官功能障碍。CLP后野生型和Rag-1（-/-）小鼠的存活曲线是重叠的，野生型组的存活率为35%，Rag-1（-/-）组的存活率为27%（不显著，P = 0.875）。使用基于多重珠粒的测定法，在CLP或假手术后8小时测量野生型和Rag-1（-/-）小鼠血浆中23种细胞因子和趋化因子的介体浓度。与假手术小鼠相比，观察到粒细胞集落刺激因子、角质形成细胞趋化因子、IL-6、单核细胞趋化蛋白1和IL-10的介体水平最高。大多数介质的水平不受T和B淋巴细胞缺乏的影响。与野生型小鼠相比，Rag-1（-/-）小鼠中仅IL-6和IL-17的浓度显著较低。总之，在CLP模型中缺乏T和B细胞似乎不会影响严重脓毒症的急性结局。
The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene 1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1(-/-) mice were atrophic and completely devoid of CD3(+) T cells and CD19(+) B cells. Wild-type mice and Rag-1(-/-) mice (both on a C57BL/6J background) underwent CLP or sham surgery. Both wild-type and Rag-1(-/-) mice developed clinical signs of sepsis within the first day after CLP. This included severe hypothermia as measured by a decrease in body surface temperature and organ dysfunction as detected by plasma increases in blood urea nitrogen and lactate dehydrogenase levels. Survival curves of wild-type and Rag-1(-/-) mice after CLP were superimposable, with 35% survival in the wild-type group and 27% survival in the Rag-1(-/-) group, respectively (not significant, P = 0.875). Using multiplex bead-based assays, the mediator concentrations for 23 cytokines and chemokines were measured in plasma of wild-type and Rag-1(-/-) mice 8 h after CLP or sham surgery. Compared with sham surgery mice, the highest mediator levels were observed for granulocyte colony-stimulating factor, keratinocyte chemoattractant, IL-6, monocyte chemotactic protein 1, and IL-10. Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1(-/-) mice compared with wild-type mice. In conclusion, the absence of T and B cells in the CLP model used does not appear to affect the acute outcome of severe sepsis.