Pregnancy-associated changes in oligomannose oligosaccharides of human and bovine uromodulin (Tamm-Horsfall glycoprotein).
The urinary glycoprotein uromodulin (Tamm-Horsfall glycoprotein) exhibits a pregnancy-associated ability to inhibit antigen-specific T cell proliferation, and the activity is associated with a carbohydrate moiety [Muchmore and Decker (1985) Science 229:479-81; Hession et al., (1987) Science 237:1479-84; Muchmore, Shifrin and Decker (1987) J Immunol 138:2547-53]. We report here that the Man6(7)GlcNAc2-R glycopeptides derived from uromodulin inhibit antigen-specific T cell proliferation by 50% at 0.2-2 microM, and further studies, reported elsewhere, confirm that oligomannose glycopeptides from other sources are also inhibitory, with Man9GlcNAc2-R the most inhibitory of those tested [Muchmore et al., J Leukocyte Biol (in press)]. In this work, we have extended the observation of pregnancy-associated inhibitory activity to a second species, and have compared the oligomannose profile of Tamm-Horsfall glycoprotein (nonpregnant) with that of uromodulin (pregnant) derived from both human and bovine sources. Surprisingly, there was a pregnancy-associated decrease in the total content of oligomannose chains due predominantly to a reduction in Man5GlcNAc2-R and Man6GlcNAc2-R. Man7GlcNAc2-R, which did not decrease with pregnancy, comprised a significantly greater proportion of the total oligomannose chains in pregnant vs. nonpregnant samples from both species (human; 34.6% vs. 25.9%: bovine; 14.4% vs. 7.2%).
Smagula
R M
RM
Department of Biochemistry, University of Maine, Orono 04469.
Van Halbeek
H
H
Decker
J M
JM
Muchmore
A V
AV
Moody
C E
CE
Sherblom
A P
AP
D000818:Animals; D002240:Carbohydrate Sequence; D002417:Cattle; D002455:Cell Division; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000378:metabolism* / Q000652:urine; D009844:Oligosaccharides / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D058949:Uromodulin
D009088:Mucoproteins; D009844:Oligosaccharides; D011257:Pregnancy Proteins; C548612:UMOD protein, human; C548613:Umod protein, mouse; D058949:Uromodulin; D008358:Mannose