The Kupffer Cell Inhibition Exacerbates but Splenectomy Prevents Mortality in a Rat Septic Peritonitis Model
The Kupffer Cell Inhibition Exacerbates but Splenectomy Prevents Mortality in a Rat Septic Peritonitis Model
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DOI：
10.1016/j.jss.2011.02.031
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发表时间：
2012-06-01
影响因子：
2.2
通讯作者：
Hosomura, Naohiro
中科院分区：
文献类型：
--
作者：
Kono, Hiroshi;Fujii, Hideki;Hosomura, Naohiro
Objective.本研究旨在探讨抑制枯否细胞（KCs）是否影响高迁移率族蛋白1（HMGB 1）的表达和脓毒性腹膜炎的死亡率。脾脏在脓毒性腹膜炎中的作用也进行了研究。在盲肠结扎和穿孔（CLP）前给予脂质体包埋的二氯亚甲基二膦酸盐（lipo-MDP）或非包埋的脂质体（lipo）清除KC，CLP后测定血清HMGB 1水平和死亡率。此外，分离KCs和组织巨噬细胞，并研究HMGB 1的产生。同时观察CLP术后脾切除对血清HMGB 1水平和死亡率的影响。Lipo-MDP清除枯否细胞后，血清HMGB 1浓度和死亡率显著升高。此外，HMGB 1在门静脉周围区域的肝脏和脾脏中的表达在lipo-MDP组中比lipo组更高。另一方面，脾切除术降低了血清HMGB 1水平，改善了CLP后的死亡率。CLP后HMGB 1在脾脏的表达高于肝脏。此外，在体外脾巨噬细胞中HMGB 1的产生最大。CLP后，未切除脾的动物中ED 3阳性细胞的数量显著增加，但切除脾的动物中ED 3阳性细胞的数量未显著增加。在脂质体-MDP治疗组中，CLP后未切除脾的动物肝脏中ED 3阳性巨噬细胞的数量也增加，但在切除脾的动物中没有增加。肝和脾在感染性腹膜炎的宿主防御中起关键作用。迁移到肝脏的巨噬细胞部分来自CLP后的脾脏。(C)2012 Elsevier Inc. All rights reserved.
Objective. The purpose of this study was to investigate whether inhibition of Kupffer cells (KCs) affects the expression of high mobility group box 1 (HMGB1) and mortality in septic peritonitis. The role of the spleen in septic peritonitis was also investigated.Methods. Rats were given liposome-entrapped dichloromethylene diphosphonate (lipo-MDP) to eliminate KCs or non-entrapped liposome (lipo) before cecal ligation and puncture (CLP), and serum HMGB1 levels and mortality were assessed after CLP. Furthermore, KCs and tissue macrophages were isolated, and production of HMGB1 was investigated. Effects of splenectomy on serum HMGB1 levels and mortality were also investigated after CLP.Results. Elimination of the Kupffer cells by lipo-MDP increased serum HMGB1 concentrations and mortality significantly. Furthermore, HMGB1 expression in both the periportal area of the liver and the spleen was greater in the lipo-MDP group than the lipo group. On the other hand, splenectomy blunted serum HMGB1 levels and improved mortality after CLP. The HMGB1 expression was greater in the spleen compared with the liver after CLP. Furthermore, production of HMGB1 was greatest in splenic macrophages in vitro. The number of ED3-positive cells increased significantly in non-splenectomized animals but not in splenectomized animals after CLP. In the lipo-MDP treated groups, the number of ED3-positive macrophages also increased in the liver from non-splenectomized animals but not in the splenectomized animals after CLP.Conclusions. The liver and the spleen play key roles in host defense during septic peritonitis. Migrating macrophages into the liver are, in part, derived from the spleen after CLP. (C) 2012 Elsevier Inc. All rights reserved.