Wang Yunlong, Zhu Xuewei, Wu Gang, Shen Le, Chen Baosheng
National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Lipid Res. 2008 Aug;49(8):1640-5. doi: 10.1194/jlr.M700446-JLR200. Epub 2008 May 5.
HDL has been shown to be able to neutralize the toxicity of lipopolysaccharide (LPS). Our previous study (J. Lipid Res. 2005. 46: 1303-1311) characterized the properties of secondary structure and in vitro functions of different cysteine mutants of apolipoprotein A-I. Here, we reconstituted recombinant HDLs (named rHDLwt, rHDL52, rHDL74, rHDL107, rHDL129, rHDL173, rHDL195, and rHDL228) by mixing wild type or those mutants with dipalmitoyl phosphatidylcholine and examined their in vivo effects on LPS-induced endotoxemia in mice. Our results showed that 24 h after injection, mice receiving rHDL74 or rHDL52 had a significant decrease of plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), compared with control mice receiving either saline or rHDLwt (P < 0.05). Administration of rHDL74 to mice injected with LPS also led to a decrease of plasma IL-6, protection of lung against acute injury, and attenuation of endotoxin-induced clinical symptoms in mice, compared with controls injected with LPS only. However, injection of rHDL228 significantly increased plasma concentration of TNF-alpha and exacerbated LPS-induced lung injury. In summary, compared with rHDLwt, rHDL74 and rHDL52 exhibit higher anti-inflammation capabilities, whereas rHDL228 shows hyper-proinflammation by exacerbating LPS-induced endotoxemia in mice.
高密度脂蛋白（HDL）已被证明能够中和脂多糖（LPS）的毒性。我们之前的研究（《脂质研究杂志》2005年。46: 1303 - 1311）对载脂蛋白A-I不同半胱氨酸突变体的二级结构特性和体外功能进行了表征。在此，我们通过将野生型或这些突变体与二棕榈酰磷脂酰胆碱混合，重构了重组高密度脂蛋白（命名为rHDLwt、rHDL52、rHDL74、rHDL107、rHDL129、rHDL173、rHDL195和rHDL228），并研究了它们对小鼠LPS诱导的内毒素血症的体内影响。我们的结果表明，注射后24小时，与接受生理盐水或rHDLwt的对照小鼠相比，接受rHDL74或rHDL52的小鼠血浆肿瘤坏死因子α（TNF-α）和白细胞介素-1β（IL-1β）显著降低（P < 0.05）。给注射LPS的小鼠施用rHDL74，与仅注射LPS的对照相比，还导致血浆IL-6降低、肺部免受急性损伤以及内毒素诱导的小鼠临床症状减轻。然而，注射rHDL228显著增加了TNF-α的血浆浓度，并加剧了LPS诱导的肺损伤。总之，与rHDLwt相比，rHDL74和rHDL52表现出更高的抗炎能力，而rHDL228通过加剧小鼠LPS诱导的内毒素血症表现出促炎作用增强。
