Hurt E, Bondjers G, Camejo G
Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Sahlgren's Hospital, Sweden.
J Lipid Res. 1990 Mar;31(3):443-54.
The aim of this work was to investigate the possible mechanisms for uptake by human monocyte-derived macrophages (HMDM) of low density lipoprotein (LDL) pretreated with human arterial chondroitin-6-SO4-rich proteoglycan (LDL-PG). HMDM were incubated with 125I-labeled tyramine cellobiose-labeled LDL-PG, native LDL, and acetylated LDL (Ac-LDL). The results showed that two to four times more LDL-PG than LDL was bound and internalized by the HMDM. Competition experiments showed that LDL-PG competed with native LDL for the apoB,E (LDL) receptor, but not for the Ac-LDL scavenger receptor. Both the LDL and LDL-PG uptake were reduced after preincubation of the macrophages with unlabeled native LDL, though to a lesser extent with LDL-PG. The specific binding of 125I-labeled LDL and 125I-labeled LDL-PG at 4 degrees C was both saturable and concentration-dependent. The dissociation constant (Kd) for binding was 8.6 x 10(-9) M for LDL and 9.4 x 10(-9) M for LDL-PG, but the maximum binding (Bmax) was 1.5-times higher for LDL-PG. Cholesterol derived from LDL-PG was less effective than native LDL in suppressing HMG-CoA reductase activity. The results indicate that the uptake of LDL-PG is mediated not only by the LDL-receptor, but also by another unspecific pathway, which may not be subjected to regulation. These results provide further support for the hypothesis that LDL modifications induced by arterial PG may contribute to the formation of foam cells.
这项工作的目的是研究人动脉富含硫酸软骨素-6的蛋白聚糖预处理的低密度脂蛋白（LDL-PG）被人单核细胞衍生巨噬细胞（HMDM）摄取的可能机制。将HMDM与125I标记的纤维二糖酪胺标记的LDL-PG、天然LDL和乙酰化LDL（Ac-LDL）一起孵育。结果显示，HMDM结合并内化的LDL-PG比LDL多两到四倍。竞争实验表明，LDL-PG与天然LDL竞争载脂蛋白B、E（LDL）受体，但不与Ac-LDL清道夫受体竞争。用未标记的天然LDL预孵育巨噬细胞后，LDL和LDL-PG的摄取均减少，不过LDL-PG减少的程度较小。4℃时125I标记的LDL和125I标记的LDL-PG的特异性结合是饱和的且呈浓度依赖性。LDL结合的解离常数（Kd）为8.6×10^(-9)M，LDL-PG为9.4×10^(-9)M，但LDL-PG的最大结合量（Bmax）高1.5倍。源自LDL-PG的胆固醇在抑制HMG-CoA还原酶活性方面比天然LDL效果差。结果表明，LDL-PG的摄取不仅由LDL受体介导，还由另一种非特异性途径介导，该途径可能不受调控。这些结果为动脉PG诱导的LDL修饰可能有助于泡沫细胞形成这一假说提供了进一步支持。
