In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure

被引:79
作者
Wright, A
Sato, Y
Okada, T
Chang, KH
Endo, T
Morrison, SL
机构
[1] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[3] Tokyo Metropolitan Inst Gerontol, Dept Glycobiol, Itabashi Ku, Tokyo 1730015, Japan
关键词
Fc carbohydrate; IgG catabolism;
D O I
10.1093/glycob/10.12.1347
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have now produced mouse-human chimeric IgG1 in wild-type Chinese hamster ovary (CHO) cell lines Pro-5 as well as in the glycosylation mutants Lec 2, Lec 8, and Lec 1. Analysis of the attached carbohydrates shows those present on IgG1-Lec1 were mannose terminated, Carbohydrate present on IgG1-Lec8 was uniformly biantennary terminating in N-acetylglucosamine. The glycosglation profiles of IgG1-Lec 2 and IgG1-Pro-5 were heterogeneous. Only IgG1-Pro-5 was sialylated with sialic acid present on only a small percentage of the carbohydrate structures. When the in vivo fate of antibodies labeled with I-125-lactotyramine was determined, it was found that the majority of all of the antibodies, irrespective of the structure of their attached carbohydrate, is catabolized in the skin and muscle. However, the attached carbohydrate structure does influence the amount that is catabolized in the liver and the liver serves as a major site for the catabolism of proteins bearing carbohydrate with the Lec2 (with terminal galactose) or Lec1 (with terminal mannose) structure.
引用
收藏
页码:1347 / 1355
页数:9
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