Mweva S, Paul J L, Cambillau M, Goudouneche D, Beaune P, Simon A, Fournier N
Service de Biochimie, Hôpital Européen Georges Pompidou, Paris, France.
Eur J Clin Invest. 2006 Aug;36(8):552-9. doi: 10.1111/j.1365-2362.2006.01673.x.
Fu5AH rat hepatoma cells and cAMP (cyclic AMP)-pretreated J774 mouse macrophages are commonly used as models for SR-BI (scavenger receptor class B type I) and ABCA1 (ATP binding cassette transporter 1)-mediated free cholesterol efflux to whole serum, respectively. However, the responsiveness of Fu5AH, control or cAMP pretreated J774 cells to the various lipids and HDL (high-density lipoprotein)-parameters from both normo- and dyslipidaemic subjects has never been compared within the same study.
Fifty-eight men were classified into four groups: type IIa hypercholesterolaemic (n = 12), type IIb dyslipidaemic (n = 13), type IV hypertriglyceridaemic (n = 18) and normolipidaemic (n = 15) were recruited. A complete lipid profile including prebeta-HDL was performed. Cholesterol efflux from Fu5AH cells as well as from control or cAMP pretreated J774 cells were measured; the difference between these two latter values being taken as the ABCA1-mediated efflux.
The Fu5AH and the control J774 cells delivered cholesterol to mature HDLs, especially to phospholipid (PL)-rich HDL. Using cAMP pretreated cells, the ABCA1-dependent efflux was highly sensitive to prebeta-HDL, which appeared to be a factor in determining the efflux. Consistent with the dependence of the SR-BI-mediated efflux on HDL-PL levels, which are not different between groups, all sera displayed similar efflux capacities from the Fu5AH cells. Conversely, in accordance with their high prebeta-HDL levels, the ABCA1-dependent efflux highlighted the efficiency of type IV sera.
Two complementary cellular models providing SR-BI and ABCA1-dependent efflux should be used to measure the capacity of a biological fluid which contains a wide variety of components to promote cholesterol efflux.
Fu5AH大鼠肝癌细胞和经环磷酸腺苷（cAMP）预处理的J774小鼠巨噬细胞通常分别用作I型清道夫受体（SR-BI）和ATP结合盒转运体A1（ABCA1）介导的游离胆固醇向全血清流出的模型。然而，在同一研究中，从未比较过Fu5AH细胞、对照或经cAMP预处理的J774细胞对来自血脂正常和血脂异常受试者的各种脂质及高密度脂蛋白（HDL）参数的反应性。
招募了58名男性，分为四组：IIa型高胆固醇血症组（n = 12）、IIb型血脂异常组（n = 13）、IV型高甘油三酯血症组（n = 18）和血脂正常组（n = 15）。进行了包括前β-HDL在内的完整血脂谱分析。测定了Fu5AH细胞以及对照或经cAMP预处理的J774细胞的胆固醇流出；后两个值之间的差异视为ABCA1介导的流出。
Fu5AH细胞和对照J774细胞将胆固醇转运至成熟HDL，尤其是富含磷脂（PL）的HDL。使用经cAMP预处理的细胞时，ABCA1依赖性流出对前β-HDL高度敏感，前β-HDL似乎是决定流出的一个因素。与SR-BI介导的流出对HDL-PL水平的依赖性一致（各组之间HDL-PL水平无差异），所有血清从Fu5AH细胞显示出相似的流出能力。相反，根据其较高的前β-HDL水平，ABCA1依赖性流出突出了IV型血清的效率。
应使用两种提供SR-BI和ABCA1依赖性流出的互补细胞模型来测量含有多种成分的生物流体促进胆固醇流出的能力。
