Pharmacokinetic and Tissue Distribution Mechanism of Mouse Recombinant Heat Shock Protein 70 in Mice
Pharmacokinetic and Tissue Distribution Mechanism of Mouse Recombinant Heat Shock Protein 70 in Mice
复制标题
重组热休克蛋白70在小鼠体内的药代动力学及组织分布机制
作者：
Seiji Takemoto;M. Nishikawa;Y. Takakura
无标题目的：探讨重组小鼠热休克蛋白70（Hsp70）在小鼠体内的药代动力学及肝细胞摄取机制。方法：小鼠静脉注射111In-Hsp70（111In-Hsp70）后测定Hsp70的组织分布和肝内定位。在 Hsp70 之前注射 CD91 配体或清道夫受体，以检查这些分子对 111In-Hsp70 分布的影响。还检测了原代小鼠肝细胞对 111In-Hsp70 的摄取。结果。静脉注射后，111In-Hsp70 迅速从循环中消除，主要被肝脏摄取。预注射 CD91 配体或清道夫受体可显着抑制肝脏摄取。肝脏构成细胞的分离揭示了肝细胞对 111In-Hsp70 的整体肝脏摄取的主要贡献。培养的肝细胞对 111In-Hsp70 的摄取受到 CD91 配体或抗 CD91 抗体的抑制。此外，皮下注射后，111In-Hsp70逐渐从注射部位消失，并在原发淋巴结中积累。结论。这些结果首次表明，静脉注射的Hsp70至少部分被CD91识别并被肝细胞消除，而皮下注射的Hsp70则有效地递送至区域淋巴结。
No HeadingPurpose.To investigate the in vivo pharmacokinetics and uptake mechanisms of recombinant mouse heat shock protein 70 (Hsp70) by hepatocytes in mice.Methods.The tissue distribution and intrahepatic localization of Hsp70 were determined after an intravenous injection of 111In-Hsp70 (111In-Hsp70) into mice. Ligands of CD91 or scavenger receptors were injected prior to Hsp70 to examine the involvement of these molecules on the distribution of 111In-Hsp70. The uptake of 111In-Hsp70 by primary mouse hepatocytes was also examined.Results.After intravenous injection, 111In-Hsp70 was rapidly eliminated from the circulation and taken up mainly by the liver. The hepatic uptake was significantly inhibited by preinjection of ligands for CD91 or scavenger receptors. The separation of liver-constituting cells revealed a major contribution of hepatocytes to the overall hepatic uptake of 111In-Hsp70. The uptake of 111In-Hsp70 by cultured hepatocytes was inhibited by a CD91 ligand or anti-CD91 anibody. In addition, after subcutaneous injection, 111In-Hsp70 gradually disappeared from the injection site and accumulated in primary lymph nodes.Conclusions.These results indicate for the first time that intravenous Hsp70 is, at least partially, recognized by CD91 and eliminated by hepatocytes, whereas subcutaneous Hsp70 is efficiently delivered to regional lymph nodes.
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影响因子：
4.4
作者：
H. Udono;P. K. Srivastava
通讯作者：
H. Udono;P. K. Srivastava
受体介导的抗原递送至巨噬细胞。
DOI：
--
发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chu,CT;Pizzo,SV
通讯作者：
Pizzo,SV
α2-巨球蛋白受体和低密度脂蛋白受体相关蛋白之间的序列同一性表明该分子是多功能受体。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Strickland,DK;Ashcom,JD;Williams,S;Burgess,WH;Migliorini,M;Argraves,WS
通讯作者：
Argraves,WS
影响因子：
15.9
作者：
Herz, J;Strickland, DK
通讯作者：
Strickland, DK
影响因子：
32.4
作者：
Basu, S;Binder, RJ;Srivastava, PK
通讯作者：
Srivastava, PK