Pregnancy-associated changes in the glycosylation of tamm-horsfall glycoprotein. Expression of sialyl Lewis(x) sequences on core 2 type O-glycans derived from uromodulin

Tamm-Horsfall glycoprotein (THP) is a major glycoprotein associated with human urine that binds pro-inflammatory cytokines and also inhibits in vitro T cell proliferation induced by specific antigens. THP derived from human pregnancy urine (designated uromodulin) has previously been shown to be 13-f...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-07, Vol.275 (29), p.21928-21938
Main Authors: Easton, R L, Patankar, M S, Clark, G F, Morris, H R, Dell, A
Format: Article
Language:English
Subjects:
Female
Glycosylation
Humans
Lewis Blood Group Antigens - chemistry
Lewis Blood Group Antigens - metabolism
Mass Spectrometry
Mucoproteins - chemistry
Mucoproteins - metabolism
Polysaccharides - chemistry
Polysaccharides - metabolism
Pregnancy - metabolism
Pregnancy Proteins - chemistry
Pregnancy Proteins - metabolism
Uromodulin
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Summary:Tamm-Horsfall glycoprotein (THP) is a major glycoprotein associated with human urine that binds pro-inflammatory cytokines and also inhibits in vitro T cell proliferation induced by specific antigens. THP derived from human pregnancy urine (designated uromodulin) has previously been shown to be 13-fold more effective as an inhibitor of antigen-induced T cell proliferation than THP obtained from other sources. Structural analysis of human THP and uromodulin has for the first time revealed that these glycoproteins are O-glycosylated. THP from nonpregnant females and males expresses primarily core 1 type O-glycans terminated with either sialic acid or fucose but not the sialyl Lewis(x) epitope. By contrast, the O-glycans linked to uromodulin include unusual core 2 type glycans terminated with one, two, or three sialyl Lewis(x) sequences. The specific association of these unusual carbohydrate sequences with uromodulin could explain its enhanced immunomodulatory effects compared with THP obtained from males and nonpregnant females. Analysis of THP from one of the pregnant females 2 months postpartum showed a reversion of the O-glycan profile to that found for a non-pregnant female. These data suggest that the glycosylation state of uromodulin could be under the regulation of steroidal hormones produced during pregnancy. The significant physiological implications of these observations are discussed.
ISSN:0021-9258
DOI:10.1074/jbc.M001534200