Gadolinium chloride inhibits lipopolysaccharide-induced mortality and in vivo prostaglandin E2 release by splenic macrophages
Gadolinium chloride inhibits lipopolysaccharide-induced mortality and in vivo prostaglandin E2 release by splenic macrophages
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DOI：
10.1016/s1091-255x(99)80072-9
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发表时间：
1999-05-01
影响因子：
3.2
通讯作者：
Flye, MW
中科院分区：
文献类型：
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作者：
Roland, CR;Nakafusa, Y;Flye, MW
单核细胞吞噬系统主要由肝脏和脾脏的组织巨噬细胞组成，产生前列腺素E-2（PGE（2）），一种脓毒症反应的调节剂。已知巨噬细胞内化氯化钆（GD），一种镧系金属，抑制吞噬功能。因此，我们研究了体内GD对脂多糖（LPS）诱导的死亡率和LPS刺激的培养脾巨噬细胞释放PGE 2的影响。在LPS攻击（30 mg/kg，间歇）前两天给予GD（7 mg/kg，静脉注射）完全防止了大鼠的均匀死亡。这种保护作用是短暂的，因为10天后用LPS再次激发一致致命。本实验室以前的工作已经建立了精氨酸浓度对体外巨噬细胞行为的关键作用。因此，为了建立反映门静脉系统内环境的培养条件，在正常和内毒素血症（LPS，10 mg/kg腹膜内）大鼠的门静脉和肝静脉中测量丙氨酸和精氨酸水平。与内毒素血症不改变的丙氨酸水平相反，在LPS攻击后，精氨酸浓度从正常大鼠的50至250 μ mol/L的范围降低到10至50 μ mol/L的范围。因此，随后在1200 μ mol/L精氨酸浓度（标准RPMI-1640中）以及反映生理精氨酸水平的浓度（改良RPMI-1640中为10和100 μ mol/L）下进行脾巨噬细胞分泌行为的体外试验。用LPS（0.025至2.5 μ g/ml）刺激连续两天体内盐水或GD注射（静脉注射7 mg/kg）后收获的大鼠脾巨噬细胞。在培养72小时时，GD组大鼠脾巨噬细胞释放PGE 2显著高于对照组（P
The monocytic phagocytic system, consisting primarily of tissue macrophages of the liver and spleen, produces prostaglandin E-2 (PGE(2)), a modulator of the septic response, Macrophages are known to internalize gadolinium chloride (GD), a lanthanide metal, which inhibits phagocytic function. Thus we studied the effect of in vivo GD on lipopolysacchride (LPS)-induced mortality and on LPS-stimulated PGE2 release by cultured splenic macrophages. GD (7 mg/kg intravenously) given on the two days prior to LPS challenge (30 mg/kg int ravenously) completely prevented the uniform mortality in rats. This protective effect was transient since rechallenge with LPS 10 days later was uniformly lethal. Previous work in this laboratory has established a critical role of arginine concentration on macrophage behavior in vitro. Therefore, to establish culture conditions reflective of the milieu within the portal venous system, alanine and arginine levels were measured in the portal and hepatic veins of normal and endotoxemic (LPS, 10 mg/kg intraperitoneally) rats. Ln contrast to alanine levels, which were not altered by endotoxemia, there was a reduction of arginine concentrations from a range of 50 to 250 mu mol/L in normal rats to a range of 10 to 50 mu mol/L after LPS challenge. Consequently subsequent in vitro assays of splenic macrophage secretory behavior were performed in concentrations of 1200 mu mol/L arginine (in standard RPMI-1640), as well as in concentrations reflective of physiologic arginine levels (10 and 100 mu mol/L in modified RPMI-1640). Rat splenic macrophages harvested after two consecutive days of either in vivo saline or GD injection (7 mg/kg intravenously) were stimulated with LPS (0.025 to 2.5 mu g/ml). At 72 hours of culture, the release of PGE2 by splenic macrophages from GD-treated rats was significantly (P