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The Journal of Immunology, 1998, 161: 1140-1145.
Copyright © 1998 by The American Association of Immunologists

IL-12 Promotes the Adhesion of NK Cells to Endothelial Selectins Under Flow Conditions1

Tadayuki Yago*,{dagger}, Mamoru Tsukuda*, Hirofumi Fukushima*, Hideyuki Yamaoka*, Kazumi Kurata-Miura{ddagger}, Tatsunari Nishi{ddagger} and Mutsuhiko Minami2,{dagger}

Departments of * Otorhinolaryngology and {dagger} Immunology and Parasitology, Yokohama City University, School of Medicine, Yokohama, Japan; and {ddagger} Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Tokyo, Japan

This study examined the adhesive interactions of peripheral blood NK cells with P- and E-selectin and analyzed the effect of IL-12 on the binding of NK cells to these selectins. P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on most resting and IL-12-activated NK cells. However, the percentage of resting NK cells bound to P-selectin-IgG was 15%, and that of activated NK cells bound to P-selectin-IgG was 65%. Furthermore, the number of IL-12-activated NK cells bound to P-selectin-transfected Chinese hamster ovary cells was significantly higher than that of resting NK cells under flow conditions. These interactions were abolished by the incubation of these NK cells with anti-PSGL-1 (PL-1) mAb. Thus, PSGL-1/P-selectin interaction is important in the binding of resting and activated NK cells to P-selectin. NK cells express sialyl-Lewisx (sLex) structure recognized by anti-sLex mAb (KM-93), and IL-12 activation of NK cells increased the mean fluorescence intensity of KM-93-reactive NK cells. Adhesion of IL-12-activated NK cells to E-selectin-transfected Chinese hamster ovary cells was stronger than that of resting NK cells under flow conditions. These interactions were reduced markedly by incubation with anti-sLex mAb. Thus, sLex is the major ligand of resting and activated NK cells for E-selectin. These findings indicate that IL-12 stimulation of NK cells promotes their adhesion activity to endothelial selectins.




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