HUMAN VERY LOW-DENSITY LIPOPROTEINS AND CHYLOMICRONS CAN PROTECT AGAINST ENDOTOXIN-INDUCED DEATH IN MICE
HUMAN VERY LOW-DENSITY LIPOPROTEINS AND CHYLOMICRONS CAN PROTECT AGAINST ENDOTOXIN-INDUCED DEATH IN MICE
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DOI：
10.1172/jci114765
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发表时间：
1990-09-01
影响因子：
15.9
通讯作者：
RAPP, JH
中科院分区：
文献类型：
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作者：
HARRIS, HW;GRUNFELD, C;RAPP, JH
内毒素血症刺激许多生理反应，包括脂质代谢紊乱。我们假设这种脂血症可能是机体对抗循环内毒素毒性作用的防御机制的一部分。我们测试了内毒素、脂蛋白和无脂蛋白血浆混合物的作用，并确定了不同浓度的人极低密度脂蛋白（VLDL）和乳糜微粒以及低密度脂蛋白（LDL）和高密度脂蛋白（HDL）以及合成脂肪乳剂SOYACAL预防小鼠内毒素诱导死亡的能力。这项研究表明，富含甘油三酯的VLDL和乳糜微粒，以及富含胆固醇的LDL和HDL，以及不含胆固醇的大豆可以防止内毒素诱导的死亡。保护需要少量的无脂蛋白血浆，并依赖于孵育时间和脂蛋白脂质的浓度。尽管有严格的技术来防止外源性内毒素污染，但10份重复的VLDL制剂中有8份含有内毒素（5，755 ± 0.001）。3，514 ng内毒素/mg甘油三酯，平均值±。SEM）使得分离无内毒素的VLDL变得困难。相反，LDL和HDL的同时制备物相对没有内毒素污染（3. ±. 3和320.+-. 319 ng/mg总胆固醇），表明VLDL的污染发生在体内，而不是在分离过程中。这些观察结果表明，在宿主防御内毒素血症和感染中，富含磷脂酰肌醇的脂蛋白的增加可能发挥作用。
Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755.+-.3,514 ng endotoxin/mg triglyceride, mean.+-.SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3.+-.3 and 320.+-.319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host''s defense against endotoxemia and infection.