title: In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure.
abstract: 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-Lec 1 were mannose terminated. Carbohydrate present on IgG1-Lec8 was uniformly biantennary terminating in N-acetylglucosamine. The glycosylation 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 (125)I-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.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics and the Molecular Biology Institute, University of California Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
authors.forename: A
authors.initials: A
authors.lastname: Wright
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: K
authors.initials: K
authors.lastname: Chang
authors.forename: T
authors.initials: T
authors.lastname: Endo
authors.forename: S
authors.initials: S
authors.lastname: Morrison
mesh_terms: D000818:Animals; D016466:CHO Cells; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D021381:Protein Transport; D011961:Receptors, Fc / Q000378:metabolism*
chemical_list: D002241:Carbohydrates; D007074:Immunoglobulin G; D011961:Receptors, Fc