Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 1908 76

Interleukin (IL)-15 plays a major role in accumulation of unique CD16(-) natural killer (NK) cells in the human endometrium, partly via selective extravasation of peripheral blood (PB) counterparts from local microvascular circulation. While IL-15 exhibits a chemotactic activity for PB CD16(-) NK cells, IL-15 attenuates their binding capacity to dermatan sulfate, the major CD62L ligand expressed on human uterine microvascular endothelial cells (HUtMVECs). These findings suggest that premature action of IL-15 interferes with CD62L-dependent tethering/rolling of PB CD16(-) NK cells on HUtMVECs, which is an early critical process of leukocyte extravasation. In this study, we investigated the mechanisms underlying the IL-15 regulation in the initial CD62L-dependent contact between PB CD16(-) NK cells and HUtMVECs. Unlike other candidate molecules, recombinant IL-15 downregulated CD62L expression on freshly isolated PB CD16(-) NK cells. IL-12 and IL-10, the two known upregulators of CD62L on CD16(-) NK cells, were not detectable in HUtMVECs and endometrial perivascular stromal cells. Binding to immobilized dermatan sulfate increased surface IL-15 receptor-alpha chain expression on CD16(-) NK cells. Under ovarian steroid stimulation, IL-15 was detectable on the surface, but not in the supernatant, of cultured HUtMVECs. Ovarian steroid-induced IL-15 expression on HUtMVECs was not attenuated by chondroitinase ABC (which degrades chondroitin sulfate-A and -C and dermatan sulfate) or sodium acetate buffer (which dissociates cytokines from their cognate receptors). These results suggest that HUtMVECs secrete a less soluble form of IL-15 into local microcirculation. Instead, HUtMVECs bear a membrane-bound form IL-15 under the influence of ovarian steroids, which may be favorable for preventing downregulation of CD62L on PB CD16(-) NK cells and facilitating their initial contact with HUtMVECs.
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PMID:Regulatory role of membrane-bound form interleukin-15 on human uterine microvascular endothelial cells in circulating CD16(-) natural killer cell extravasation into human endometrium. 2390 14