Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response - Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures
Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response - Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures
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DOI：
10.1172/jci118345
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发表时间：
1995-12-01
影响因子：
15.9
通讯作者：
Navab, M
中科院分区：
文献类型：
--
作者：
VanLenten, BJ;Hama, SY;Navab, M
我们先前报道，高密度脂蛋白(HDL)可以保护动脉壁细胞对低密度脂蛋白(LDL)的氧化修饰，使这些细胞产生促炎分子。我们还报道了与高密度脂蛋白相关的酶系统对高密度脂蛋白的这种抗炎作用。现在我们报道了在人类和巴豆油兔模型中，在急性时相反应(APR)之前和期间的研究。在兔模型中，从急性时相反应(APR)开始，高密度脂蛋白的保护作用逐渐减弱，到第三天完全消失，因为急性时相高密度脂蛋白(AP-HDL)中的血清淀粉样蛋白A(SAA)水平上升，载脂蛋白A-I水平下降73%，同时，高密度脂蛋白(HDL1)中对氧磷酶(PON)和血小板激活因子乙酰水解酶(PAF-AH)水平分别下降71%和90%，从第1天到第3天，第3天后，高密度脂蛋白的保护作用有所恢复，但正常或对照高密度脂蛋白(C-高密度脂蛋白)的保护作用有所恢复。在急性期极低密度脂蛋白或低密度脂蛋白中未见铜蓝蛋白的增加，纯化的低密度脂蛋白与重分离的高密度脂蛋白共同孵育后，C-HL失去了抑制低密度脂蛋白氧化的能力。Northern印迹分析显示，与C-高密度脂蛋白相比，经AP-高密度脂蛋白和CP-高密度脂蛋白处理的共培养细胞MCP-1的表达增强，经纯化的PON或PAF-AH浓缩的人AP-高密度脂蛋白对低密度脂蛋白的修饰具有保护作用。我们得出结论，在基础条件下，高密度脂蛋白具有抗炎作用，但在APR期间，与高密度脂蛋白相关的蛋白质的置换和/或交换导致了促炎分子的产生。
We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL, We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model, In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three, As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%, Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three, After day three, there was some recovery of the protective effect of HDL, AP-HDL from human patients and rabbits but not normal or control HDL(C-HDL) exhibited increases in ceruloplasmin (CP), This increase in CP was not seen in acute phase VLDL or LDL, C-HL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation, Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL, Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification, We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule.