BLOCKADE OF LIVER MACROPHAGES BY GADOLINIUM CHLORIDE REDUCES LETHALITY IN ENDOTOXEMIC RATS - ANALYSIS OF MECHANISMS OF LETHALITY IN ENDOTOXEMIA
BLOCKADE OF LIVER MACROPHAGES BY GADOLINIUM CHLORIDE REDUCES LETHALITY IN ENDOTOXEMIC RATS - ANALYSIS OF MECHANISMS OF LETHALITY IN ENDOTOXEMIA
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DOI：
10.1002/jlb.55.6.723
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发表时间：
1994-06-01
影响因子：
5.5
通讯作者：
MATSUMOTO, Y
中科院分区：
文献类型：
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作者：
IIMURO, Y;YAMAMOTO, M;MATSUMOTO, Y
我们在致死性内毒素休克大鼠模型系统[10 mg/kg体重脂多糖（LPS）静脉注射]中研究了氯化钆（GdCl3.6H（2）O）（可阻断肝巨噬细胞的吞噬作用）对死亡率、血液肿瘤坏死因子（TNF）水平和肝毒性的影响。GdCl（3）以0.5或5 mg/kg剂量两次给药，LPS注射后24 h的存活率分别为56%和100%，而血中TNF水平不受影响。肝脏的显微镜检查显示，内毒素血症下肝细胞的局灶性坏死完全受到5 mg/kg GdCl 3给药的保护。然后，我们研究了GdCl 3对离体肝巨噬细胞产生超氧阴离子（O-2（-））的影响。GdCl_3抑制对照大鼠肝巨噬细胞产生O-2（-），并呈剂量依赖性。GdCl 3对巨噬细胞也有细胞毒性作用。GdCl_3（5 mg/ kg）预处理可抑制从亚致死性内毒素血症（1 mg/kg）大鼠分离的肝巨噬细胞产生O-2（-）。有人认为，内毒素血症的致死性不能仅用血液TNF水平增加的程度来解释，并且GdCl 3降低内毒素血症死亡率和肝毒性的机制可能包括抑制肝巨噬细胞产生超氧化物。
We investigated the effects of gadolinium chloride (GdCl3.6H(2)O), which blocks phagocytosis by liver macrophages, on the mortality, blood tumor necrosis factor (TNF) levels, and hepatotoxicity in a lethal endotoxic shock rat model system [10 mg/kg body weight lipopolysaccharide (LPS) intravenously]. With administration of Gdcl(3), twice at 0.5 or 5 mg/kg, the survival rate 24 h after LPS injection was 56% and 100%, respectively, whereas the level of TNF in blood was not affected. Microscopic investigation of the liver revealed that the focal necrosis of hepatocytes under endotoxemia was completely protected by the administration of GdCl3 at 5 mg/kg. We then investigated the effects of GdCl3 on superoxide (O-2(-)) production by isolated liver macrophages in vitro. The O-2(-) production by liver macrophages isolated from control rats was suppressed by GdCl3 in a dose-dependent manner. GdCl3 also had a cytotoxic effect on these macrophages. The enhanced O-2(-) production by liver macrophages isolated from sublethal endotoxemic (1 mg/kg) rats was suppressed by pretreatment with GdCl3 (5 mg/ kg). It was suggested that lethality in endotoxemia cannot be explained only by the degree of increase in blood TNF levels and that the mechanism by which GdCl3 reduces mortality and hepatotoxicity in endotoxemia possibly includes suppression of superoxide production by liver macrophages.