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31 July 2013 Regulatory Role of Membrane-Bound Form Interleukin-15 on Human Uterine Microvascular Endothelial Cells in Circulating CD16(−) Natural Killer Cell Extravasation into Human Endometrium
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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.

Kotaro Kitaya and Tadahiro Yasuo "Regulatory Role of Membrane-Bound Form Interleukin-15 on Human Uterine Microvascular Endothelial Cells in Circulating CD16(−) Natural Killer Cell Extravasation into Human Endometrium," Biology of Reproduction 89(3), (31 July 2013). https://doi.org/10.1095/biolreprod.113.111138
Received: 28 May 2013; Accepted: 1 July 2013; Published: 31 July 2013
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