Dermatan sulfate proteoglycan biglycan as a potential selectin L/CD44 ligand involved in selective recruitment of peripheral blood CD16(−) natural killer cells into human endometrium

Abstract

Unique CD16(-) NK cells acutely increase in the human uterine endometrium after ovulation. The origin of these NK cells remains unknown, but they may be recruited selectively from the circulation. Proteoglycans and their glycosaminoglycan side-chains expressed on endometrial microvascular endothelial cells play a key role in lymphocyte tethering/rolling, the initial step of lymphocyte extravasation. In this study, we sought for the potential proteoglycans involved in tethering/rolling of peripheral blood CD16(-) NK cells on endometrial microvascular endothelial cells. As compared with CD16(+) NK cells and non-NK cells, enriched peripheral blood CD16(-) NK cells bound preferably to immobilized glycosaminoglycans except for keratan sulfate. CD16(-) NK cells bound maximally to dermatan sulfate (DS), which was diminished by enzymatic pretreatment with dermatanase and chondroitinase ABC, but not with chondroitinase ACII. The binding capacity of CD16(-) NK cells to DS was attenuated by blocking antibodies against selectin L and CD44 or pretreatment of CD16(-) NK cells with IL-15. Of three known DS proteoglycans, biglycan and decorin but not epiphycan were expressed in the human cycling endometrium. In the endometrial microvessels, the immunoreactivity for biglycan was greater in the secretory phase than in the proliferative phase, and there was little, if any, immunoreactivity for decorin throughout the menstrual cycle. The ovarian steroid progesterone enhanced biglycan expression in cultured human uterine microvascular endothelial cells. These findings demonstrated that DS proteoglycan biglycan is a potential selectin L/CD44 ligand involved in tethering/rolling of peripheral blood CD16(-) NK cells on endometrial microvascular endothelial cells.