In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure
In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure
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DOI：
10.1093/glycob/10.12.1347
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发表时间：
2000-12-01
期刊：
影响因子：
4.3
通讯作者：
Morrison, SL
中科院分区：
文献类型：
--
作者：
Wright, A;Sato, Y;Morrison, SL
我们现在已经在野生型中国仓鼠卵巢 (CHO) 细胞系 Pro-5 以及糖基化突变体 Lec 2、Lec 8 和 Lec 1 中产生了小鼠-人嵌合 IgG1。对所连接的碳水化合物的分析显示，IgG1-Lec1 上存在的碳水化合物以甘露糖为末端，IgG1-Lec8 上存在的碳水化合物均以 N-乙酰氨基葡萄糖为双触角末端。 IgG1-Lec 2 和 IgG1-Pro-5 的糖化谱是异质的。仅 IgG1-Pro-5 被仅存在于一小部分碳水化合物结构上的唾液酸唾液酸化。当确定 I-125-乳酪胺标记的抗体的体内命运时，发现所有抗体中的大多数，无论其附着的碳水化合物的结构如何，都会在皮肤和肌肉中分解代谢。然而，附着的碳水化合物结构确实会影响肝脏中分解代谢的量，并且肝脏是具有 Lec2（带有末端半乳糖）或 Lec1（带有末端甘露糖）结构的碳水化合物蛋白质分解代谢的主要场所。
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.