Nakamura T, Yuasa H, Watanabe J
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Biol Pharm Bull. 2000 Jun;23(6):743-7. doi: 10.1248/bpb.23.743.
The uptake of fractionated heparin was examined in the absence and presence of anionic proteins such as acetylated low density lipoprotein (Ac-LDL) and maleylated bovine serum albumin (Mal-BSA) to characterize the scavenger receptors involved in the uptake of fractionated heparin in isolated rat Kupffer cells. The uptake of fractionated heparin was completely inhibited by Ac-LDL and dextran sulfate, but only partially by Mal-BSA. Kinetic analysis revealed that the binding capacity (Bmax) of the Mal-BSA-insensitive receptor was significantly larger than that of the Mal-BSA-sensitive one, though their dissociation constants (Kd) were not significantly different. The apparent internalization rate constant (kint,app) was significantly larger for the Mal-BSA-sensitive receptor than for the Mal-BSA-insensitive one. Thus, the scavenger receptors involved in the uptake of fractionated heparin in Kupffer cells can be classified into two types, in terms of sensitivity to Mal-BSA. Mal-BSA-sensitive receptors have been characterized in macrophages and classified as class A. The Mal-BSA-sensitive one found in Kupffer cells in this study may belong to class A, while the Mal-BSA-insensitive one has been little characterized elsewhere.
在有无阴离子蛋白(如乙酰化低密度脂蛋白(Ac-LDL)和马来酰化牛血清白蛋白(Mal-BSA))存在的情况下,检测了分级肝素的摄取情况,以表征分离的大鼠库普弗细胞中参与分级肝素摄取的清道夫受体。分级肝素的摄取被Ac-LDL和硫酸葡聚糖完全抑制,但仅被Mal-BSA部分抑制。动力学分析表明,Mal-BSA不敏感受体的结合容量(Bmax)显著大于Mal-BSA敏感受体,尽管它们的解离常数(Kd)没有显著差异。Mal-BSA敏感受体的表观内化速率常数(kint,app)显著大于Mal-BSA不敏感受体。因此,就对Mal-BSA的敏感性而言,库普弗细胞中参与分级肝素摄取的清道夫受体可分为两种类型。Mal-BSA敏感受体已在巨噬细胞中得到表征并归类为A类。本研究在库普弗细胞中发现的Mal-BSA敏感受体可能属于A类,而Mal-BSA不敏感受体在其他地方几乎没有得到表征。