Glycodelin and amniotic fluid transferrin as inhibitors of E-selectin-mediated cell adhesion.
Human amniotic fluid contains a variety of glycoproteins. Several of these substances have been shown to exert immunomodulatory effects. Glycodelin, previously known as placental protein 14, is one of these glycoproteins. It has a unique carbohydrate configuration, consistent with fucosylated LacdiNAc structures that are very unusual for mammals. Oligosaccharides with fucosylated LacdiNAc antennae have previously been shown to block selectin-mediated cell adhesion. Another glycoprotein, human transferrin, is also present in amniotic fluid in relatively high concentrations. This transferrin shows a different glycosylation compared with serum transferrin. Amniotic fluid transferrin carries sialylated Lewis X antigens. Glycodelin and transferrin were isolated from amniotic fluid and for comparison from serum of pregnant women by chromatographic methods. The purified proteins were used as ligands to block E-selectin-mediated HepG2 cell adhesion. Two types of binding assays with distinct receptor accommodations (immobilised E-selectin and activated HUVECs) were used to quantify inhibition efficiencies of the different proteins. We found that glycodelin is a strong inhibitor with a 10(3)-fold potency compared to the monovalent tetrasaccharide sialyl Lewis X whereas the potency of transferrin is rather low.
Jeschke
Udo
U
Ludwig Maximilians University of Munich, Department of Obstetrics and Gynaecology, Maistrasse 11, 80337 Munich, Germany. udo.jeschke@fk-i.med.uni-muenchen.de
Wang
Xiaoyu
X
Briese
Volker
V
Friese
Klaus
K
Stahn
Renate
R
D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D019040:E-Selectin / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D016256:Lewis X Antigen / Q000378:metabolism; D011247:Pregnancy / Q000097:blood; D011257:Pregnancy Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D014168:Transferrin / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*
D004338:Drug Combinations; D019040:E-Selectin; D000071816:Glycodelin; D006023:Glycoproteins; D016256:Lewis X Antigen; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D014168:Transferrin