Ismail N A, Alavi M Z, Moore S
Department of Pathology, McGill University, Montreal, Canada.
Pathology. 1994 Apr;26(2):145-53. doi: 10.1080/00313029400169391.
Lipoprotein-Proteoglycan (LP-PG) complexes from the neointima, developed in response to injury, were studied to examine their ability to stimulate lipid accumulation in blood monocyte-derived macrophages (BMDM). LP-PG complexes were extracted from intimal-medial tissues from normal and balloon catheter deendothelialized aortas of normocholesterolemic rabbits, in 0.16 M NaCl for 24 h at 4 degrees C. The extract was purified through an anti-apo-B affinity column. Adsorbed material dissociated with 4 M Gu-HCI buffer was analyzed for lipoproteins (LP) and glycosaminoglycans (GAG). Results demonstrated that LP-PG complexes consisted of apo-B associated with chondroitin sulfate and hyaluronic acid. BMDM were incubated with 125I-LP, 125I-LP-NPG (from normal aortas) or 125I-LP-IPG (from injured aortas) for 20 h at 37 degrees C. LP binding, internalization and degradation was markedly increased for LP-NPG and LP-IPG over native LP. Phagocytosis appeared to be the primary route of uptake of LP-PG complexes. Competition experiments indicated that about 40% of the uptake of LP-PG complexes is mediated by the apo-B/E receptor pathway. The scavenger receptor played a minor part in the uptake of LP-PG complexes. Data from this study indicate that LP-PG complexes are present in normal and injured aortas of normocholesterolemic rabbits and these complexes accelerate LP uptake by BMDM more than native LP. Therefore, LP-PG complexes may contribute to lipid accumulation by BMDM, thus generating foam cells. Furthermore, LP-PG complexes prepared from PG of injured aortas are more effective in lipid accumulation than LP-PG complexes from PG of normal aortas.
研究了因损伤而在新生内膜中形成的脂蛋白 - 蛋白聚糖（LP - PG）复合物，以检验其刺激血液单核细胞衍生巨噬细胞（BMDM）脂质积累的能力。从正常和经球囊导管去内皮的正常胆固醇血症兔主动脉的内膜 - 中膜组织中提取LP - PG复合物，在0.16 M NaCl中于4℃下提取24小时。提取物通过抗载脂蛋白B亲和柱纯化。用4 M盐酸胍缓冲液解离吸附的物质，分析其中的脂蛋白（LP）和糖胺聚糖（GAG）。结果表明，LP - PG复合物由与硫酸软骨素和透明质酸相关的载脂蛋白B组成。将BMDM与125I - LP、125I - LP - NPG（来自正常主动脉）或125I - LP - IPG（来自损伤主动脉）在37℃下孵育20小时。与天然LP相比，LP - NPG和LP - IPG的LP结合、内化和降解明显增加。吞噬作用似乎是LP - PG复合物摄取的主要途径。竞争实验表明，LP - PG复合物摄取的约40%由载脂蛋白B/E受体途径介导。清道夫受体在LP - PG复合物的摄取中起次要作用。本研究数据表明，LP - PG复合物存在于正常胆固醇血症兔的正常和损伤主动脉中，并且这些复合物比天然LP更能加速BMDM对LP的摄取。因此，LP - PG复合物可能有助于BMDM的脂质积累，从而产生泡沫细胞。此外，由损伤主动脉的蛋白聚糖制备的LP - PG复合物在脂质积累方面比正常主动脉的蛋白聚糖制备的LP - PG复合物更有效。
