Purification and characterization of an immunomodulatory endometrial protein, glycodelin

Human glycodelin is synthesized by endometrial cells in the late secretory phase and early pregnancy under hormonal regulation. Whereas the precise ph ysiological functions of glycodelin are unknown, its expression during embr yonic nidation and its inhibition of T cell proliferation suggest an immuno modulatory role. We purified human glycodelin from first trimester human de cidual cytosol by using a rapid two-step high-performance liquid chromatogr aphy method and investigated its effects on human monocyte migration. Human U931 cells were used as a model of monocyte chemotaxis in Hoyden chamber m igration assays. N-Formyl-Met-Leu-Phe and the beta -chemokine RANTES (regul ated on activation normal T cell expressed and secreted) were used as monoc yte chemoattractants. Purified glycodelin inhibited monocyte migration in a dose-dependent fashion (IC50 = 550 nM). Glycodelin activity was totally re versed by heat inactivation (95 degreesC x 15 min) and neutralized by pretr eatment with specific anti-glycodelin antibodies. Deglycosylated glycodelin was equipotent to intact glycodelin in the monocyte migration assay. I-125 -Glycodelin binding to whole U931 cells revealed a single, saturable site w ith a K-d = 48 +/- 21 nM by Scatchard analysis. Cross-linking studies indic ated that glycodelin binds to a high molecular mass (similar to 250 kDa) pr otein complex at the monocyte cell surface. Our findings support the hypoth esis that glycodelin reduces the local maternal inflammatory response towar d the implantation of a semiallogeneic conceptus.