Seo T, St Clair R W
Department of Pathology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1072, USA.
J Lipid Res. 1997 Apr;38(4):765-79.
Pigeon and rabbit beta-migrating very low density lipoprotein (beta-VLDL) are similar in size and composition, yet rabbit beta-VLDL consistently stimulates greater cholesteryl ester accumulation in pigeon peritoneal macrophages than does pigeon beta-VLDL. The purpose of this study was to determine the mechanism of this difference. Pigeon beta-VLDL bound to both a high and low affinity site while rabbit beta-VLDL bound primarily to a low affinity site. The high affinity site had the characteristics of the LDL receptor. Most rabbit beta-VLDL and some pigeon beta-VLDL bound to the low affinity site that was not down-regulated by cholesterol loading. beta-VLDL binding to the low affinity site and subsequent internalization and degradation were mediated by cell surface heparan sulfate proteoglycans (HSPG). Evidence for this includes inhibition of binding and uptake by chlorate, which prevents sulfation of proteoglycans, and by treatment with heparinase but not chondroitinase ABC. beta-VLDL uptake was stimulated by lipoprotein lipase (LpL) and apolipoprotein E (apoE), both known to bind HSPGs. Uptake and degradation of beta-VLDL were not mediated by the LDL receptor or the alpha(2)MR/LRP. Thus, binding of beta-VLDL to low affinity, high capacity HSPG binding sites on pigeon macrophages appears to directly promote internalization and degradation and is largely responsible for the greater ability of rabbit beta-VLDL to stimulate cholesterol accumulation.
鸽和兔的β-迁移极低密度脂蛋白（β-VLDL）在大小和组成上相似，但兔β-VLDL在鸽腹膜巨噬细胞中持续刺激产生的胆固醇酯积累比鸽β-VLDL更多。本研究的目的是确定这种差异的机制。鸽β-VLDL与高亲和力和低亲和力位点均结合，而兔β-VLDL主要与低亲和力位点结合。高亲和力位点具有低密度脂蛋白受体的特征。大多数兔β-VLDL和一些鸽β-VLDL与低亲和力位点结合，该位点不会因胆固醇负荷而下调。β-VLDL与低亲和力位点的结合以及随后的内化和降解由细胞表面硫酸乙酰肝素蛋白聚糖（HSPG）介导。这方面的证据包括氯酸盐抑制结合和摄取，氯酸盐可阻止蛋白聚糖的硫酸化，以及用肝素酶而非软骨素酶ABC处理。脂蛋白脂肪酶（LpL）和载脂蛋白E（apoE）均能刺激β-VLDL的摄取，已知它们都能与HSPG结合。β-VLDL的摄取和降解不是由低密度脂蛋白受体或α2MR/LRP介导的。因此，β-VLDL与鸽巨噬细胞上低亲和力、高容量的HSPG结合位点的结合似乎直接促进了内化和降解，并且在很大程度上导致了兔β-VLDL刺激胆固醇积累的能力更强。
