First Department of Surgery, University of Yamanashi, Yamanashi, Japan.
J Surg Res. 2012 Jun 1;175(1):101-12. doi: 10.1016/j.jss.2011.02.031. Epub 2011 Mar 21.
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.
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.
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.
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.
本研究旨在探讨枯否细胞（KCs）抑制对脓毒症性腹膜炎中高迁移率族蛋白 1（HMGB1）表达和死亡率的影响。同时还研究了脾脏在脓毒症性腹膜炎中的作用。
在盲肠结扎穿孔（CLP）前，大鼠给予脂多糖包被二氯亚甲基二磷酸酯（lipo-MDP）以消除 KCs 或未包被的脂质体（lipo），并在 CLP 后评估血清 HMGB1 水平和死亡率。此外，分离 KCs 和组织巨噬细胞，研究 HMGB1 的产生。还研究了 CLP 后脾切除对血清 HMGB1 水平和死亡率的影响。
lipo-MDP 消除 KCs 可显著增加血清 HMGB1 浓度和死亡率。此外，lipo-MDP 组肝门静脉周围区和脾脏的 HMGB1 表达均高于 lipo 组。另一方面，CLP 后脾切除可使血清 HMGB1 水平降低，死亡率提高。CLP 后，脾脏的 HMGB1 表达大于肝脏。此外，体外培养时，脾巨噬细胞产生的 HMGB1 最多。CLP 后，非脾切除动物的 ED3 阳性细胞数显著增加，但脾切除动物则无此增加。在 lipo-MDP 处理组中，CLP 后非脾切除动物的肝脏中 ED3 阳性巨噬细胞的数量也增加，但脾切除动物则无此增加。
在脓毒症性腹膜炎中，肝脏和脾脏在宿主防御中起关键作用。CLP 后，进入肝脏的迁移巨噬细胞部分来源于脾脏。
