title: Regulatory role of membrane-bound form interleukin-15 on human uterine microvascular endothelial cells in circulating CD16(-) natural killer cell extravasation into human endometrium.
abstract: 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.
authors.affiliation: Department of Anatomy and Cell Science, Kansai Medical University, Moriguchi, Osaka, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kitaya
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Yasuo
mesh_terms: D000328:Adult; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004717:Endometrium / Q000098:blood supply* / Q000166:cytology / Q000276:immunology; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D055806:Microvessels / Q000166:cytology / Q000502:physiology; D017452:Receptors, IgG / Q000378:metabolism; D057688:Transcellular Cell Migration; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D014599:Uterus / Q000098:blood supply / Q000166:cytology* / Q000276:immunology
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D019409:Interleukin-15; D017452:Receptors, IgG
keywords: CD62L; IL-15; NK cell; chemokine; chemotaxis; dermatan sulfate; endometrium; implantation; reproductive immunology; uterine microvascular endothelial cells; uterus