FORMALDEHYDE TREATED ALBUMIN CONTAINS MONOMERIC AND POLYMERIC FORMS THAT ARE DIFFERENTLY CLEARED BY ENDOTHELIAL AND KUPFFER CELLS OF THE LIVER - EVIDENCE FOR SCAVENGER RECEPTOR HETEROGENEITY

FORMALDEHYDE TREATED ALBUMIN CONTAINS MONOMERIC AND POLYMERIC FORMS THAT ARE DIFFERENTLY CLEARED BY ENDOTHELIAL AND KUPFFER CELLS OF THE LIVER - EVIDENCE FOR SCAVENGER RECEPTOR HETEROGENEITY
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DOI:
10.1016/s0006-291x(05)81249-5
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发表时间:
1991-10-15
影响因子:
3.1
通讯作者:
MEIJER, DKF
MEIJER, DKF
中科院分区:
生物学4区
文献类型:
--
作者:
JANSEN, RW;MOLEMA, G;MEIJER, DKF

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甲醛处理的白蛋白(F-HSA)被发现由单体和聚合部分组成。两组分均主要被大鼠肝窦细胞内吞。然而,内吞物质的免疫组织化学染色显示内皮细胞和库普弗细胞对单体和聚合物摄取的相对贡献有显著差异,单体主要有内皮细胞,而聚合物主要有库普弗细胞分布模式。为了直接证实这些异质性模式,我们在体内注射了125i标记的F-HSA部分,并通过离心洗脱分离内皮细胞和Kupffer细胞。在内皮细胞中发现了73.7%的单体F-HSA,而在库普弗细胞中仅发现了14.9%。相比之下,聚合F-HSA (1500 kD)主要被库普弗细胞(71%)内吞,而内皮细胞仅贡献24%的肝摄取。体内研究和离体灌注大鼠肝脏实验表明,多肌苷酸(一种众所周知的清道夫受体抑制剂)共同给药可抑制单体和聚合物的内吞作用,表明内皮细胞和库普弗细胞上的这些受体主要参与了这一摄取过程。
Formaldehyde treated albumin (F-HSA) was found to consist of a monomeric and a polymeric fraction. Both fractions were primarily endocytosed by rat liver sinusoidal cells. However, immunohistochemical staining of endocytosed material showed that the relative contribution of the endothelial and Kupffer cells in uptake of the monomer and the polymer differed significantly, with the monomer mainly having an endothelial cell- and the polymer predominantly having a Kupffer cell pattern of distribution. To directly confirm these heterogeneous patterns, we injected in vivo the125I-labeled F-HSA fractions and isolated the endothelial and Kupffer cells by centrifugal elutriation. 73.7% of the monomeric F-HSA was found in endothelial cells and only 14.9% was found in Kupffer cells. In contrast, the polymeric F-HSA (1500 kD) was mainly endocytosed by Kupffer cells (71%), whereas the endothelial cells contributed only for 24% in hepatic uptake. In vivo studies and isolated perfused rat liver experiments showed that endocytosis of both monomer and polymer was inhibited by co-administration of polyinosinic acid, a well known inhibitor for scavenger receptors, indicating that these receptors on endothelial and Kupffer cells are mainly involved in this uptake process.