Effects of differential glycosylation of glycodelins on lymphocyte survival.
Glycodelin is a human glycoprotein with four reported glycoforms, namely glycodelin-A (GdA), glycodelin-F (GdF), glycodelin-C (GdC), and glycodelin-S (GdS). These glycoforms have the same protein core and appear to differ in their N-glycosylation. The glycosylation of GdA is completely different from that of GdS. GdA inhibits proliferation and induces cell death of T cells. However, the glycosylation and immunomodulating activities of GdF and GdC are not known. This study aimed to use ultra-high sensitivity mass spectrometry to compare the glycomes of GdA, GdC, and GdF and to study the relationship between the immunological activity and glycosylation pattern among glycodelin glycoforms. Using MALDI-TOF strategies, the glycoforms were shown to contain an enormous diversity of bi-, tri-, and tetra-antennary complex-type glycans carrying Galbeta1-4GlcNAc (lacNAc) and/or GalNAcbeta1-4GlcNAc (lacdiNAc) antennae backbones with varying levels of fucose and sialic acid substitution. Interestingly, they all carried a family of Sda (NeuAcalpha2-3(GalNAcbeta1-4)Gal)-containing glycans, which were not identified in the earlier study because of less sensitive methodologies used. Among the three glycodelins, GdA is the most heavily sialylated. Virtually all the sialic acid on GdC is located on the Sda antennae. With the exception of the Sda epitope, the GdC N-glycome appears to be the asialylated counterpart of the GdA/GdF glycomes. Sialidase activity, which may be responsible for transforming GdA/GdF to GdC, was detected in cumulus cells. Both GdA and GdF inhibited the proliferation, induced cell death, and suppressed interleukin-2 secretion of Jurkat cells and peripheral blood mononuclear cells. In contrast, no immunosuppressive effect was observed for GdS and GdC.
Lee
Cheuk-Lun
CL
Department of Obstetrics and Gynaecology and Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, China.
Pang
Poh-Choo
PC
Yeung
William S B
WS
Tissot
Bérangère
B
Panico
Maria
M
Lao
Terence T H
TT
Chu
Ivan K
IK
Lee
Kai-Fai
KF
Chung
Man-Kin
MK
Lam
Kevin K W
KK
Koistinen
Riitta
R
Koistinen
Hannu
H
Seppälä
Markku
M
Morris
Howard R
HR
Dell
Anne
A
Chiu
Philip C N
PC
D017209:Apoptosis; D002236:Carbohydrate Conformation; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D054885:Cumulus Cells / Q000201:enzymology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D000071816:Glycodelin; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009336:Necrosis / Q000473:pathology; D009439:Neuraminidase / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry; D011257:Pregnancy Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000071816:Glycodelin; D006023:Glycoproteins; D007376:Interleukin-2; D037102:Lectins; C045246:PAEP protein, human; D011134:Polysaccharides; D011257:Pregnancy Proteins; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid