Binding kinetics of monomeric and aggregated IgG to Kupffer cells and hepatocytes of mice.

Binding kinetics of monomeric and aggregated IgG to Kupffer cells and hepatocytes of mice.
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单体和聚集 IgG 与小鼠库普弗细胞和肝细胞的结合动力学。

DOI:
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发表时间:
1984
期刊:
影响因子:
6.4
通讯作者:
J. Egido
J. Egido
中科院分区:
医学2区
文献类型:
--
作者:
J. Sancho;E. González;J. Escanero;J. Egido

文献摘要

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本文研究了人单体IgG和稳定热聚集IgG(A-IgG)与小鼠肝细胞和枯否细胞Fc受体的结合动力学。注射放射性标记蛋白后,在实质细胞(肝细胞)中回收了60-70%的肝摄取。在体外实验中,与单体IgG相比,A-IgG与肝细胞和枯否细胞的结合量更大。枯否细胞聚集体的结合速率常数略高于肝细胞,而枯否细胞聚集体的摄取百分比仅为肝细胞的5-15%。与单体IgG的1-2 X 10(7)M-1的平衡常数相比,A-IgG与两种细胞结合的聚集体的平衡常数为0.4-1 X 10(8)M-1。每个细胞结合的IgG和A-IgG分子的最大数量在肝细胞上(平均14 × 10(6))高于枯否细胞(平均2 × 10(5)),这与体内和体外实验中观察到的肝细胞对这些蛋白质的较高结合能力一致。竞争受体结合的能力似乎仅存在于IgG的Fc部分,因为IgG的F(ab ')2片段不能抑制标记的单体IgG或A-IgG。该受体似乎对IgG具有特异性,因为未标记的单体伊加显示标记的IgG或A-IgG对肝细胞和枯否细胞没有结合抑制作用。总体结果进一步表明,肝细胞可能通过Fc受体与单核吞噬细胞系统在清除循环免疫复合物中发挥协同作用。
The binding kinetics of human monomeric IgG and stable heat-aggregated IgG (A-IgG) to Fc receptors of hepatocytes and Kupffer cells isolated from mice was studied. After injection of radiolabelled proteins the 60-70% of hepatic uptake was recovered in parenchymal cells (hepatocytes). In experiments in vitro the A-IgG bound in larger amounts to hepatocytes and Kupffer cells than monomeric IgG. The association rate constants of aggregates were somewhat higher for Kupffer cells than for hepatocytes whereas the percentage uptake of aggregates by Kupffer cells was only 5-15% of that of hepatocytes. The equilibrium constants of aggregates binding to both cells amounted to 0.4-1 X 10(8) M-1 for A-IgG compared with an equilibrium constant for monomeric IgG of 1-2 X 10(7)M-1. The maximum number of IgG and A-IgG molecules bound per cell was higher on hepatocytes (mean 14 X 10(6)) than on Kupffer cells (mean 2 X 10(5)) which is in agreement with the higher binding capacity of hepatocytes for these proteins observed in vivo and in vitro experiments. The ability to compete for receptor binding seemed to reside exclusively in the Fc portion of IgG since F(ab')2 fragments of IgG failed to inhibit labelled monomeric IgG or A-IgG. The receptor seems to be specific for IgG since unlabelled monomeric IgA demonstrated no binding inhibition of labelled IgG or A-IgG on hepatocytes and Kupffer cells. The overall results further suggest that hepatocytes might through Fc receptors play a collaborative role with the mononuclear phagocytic system in the clearance of circulating immune complexes.