start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=3 article-no= start-page=508 end-page=513 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20080630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induction of cytolytic activity and interferon-gamma production in murine natural killer cells by polymyxins B and E en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Natural killer (NK) cells are the primary effector cells of the innate immune system and have well-established roles in tumor rejection and resistance to viruses, bacteria and certain parasites. There is a need for more specific immune modulators of NK cell activity that tack the wide-ranging side effects of NK cell-stimulatory interleukins. The polycationic antibiotic polymyxin B (PMB) has been shown to have a unique ability to enhance activities of some immune cells, independent of its antibiotic properties. Here we report that both PMB and its analog potymyxin E (PME) markedly enhanced the activity of NK cells enriched from the murine spleen. Maximal activation of NK cell activity was obtained after 24 h of incubation with PMB at a dose of 300 mu g/ml. PMB nonapeptide, one of the two PMB domains, and PME methanesulfonate, the negatively charged derivative of PME, had little effect on NK cell activity. PMB induced interferon (IFN)-gamma and tumor necrosis factor-a production in NK cells. Proliferation of NK cells in vitro was significantly stimulated by being incubated with PMB. Administration of PMB to mice for 7 consecutive days stimulated splenic NK cell activity and increased NK cell populations in the spleen. These results suggest that the polycationic antibiotics PMB and PME may up-regulate innate and adaptive immune responses by induction of NK cell activity and IFN-gamma production.

en-copyright= kn-copyright= en-aut-name=ZhongMing en-aut-sei=Zhong en-aut-mei=Ming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KadotaYusuke en-aut-sei=Kadota en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimizuYoshio en-aut-sei=Shimizu en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GohdaEiichi en-aut-sei=Gohda en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Bizen Chemical Co., Ltd affil-num=4 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=polymyxin B (PMB) kn-keyword=polymyxin B (PMB) en-keyword=polymyxin E (PME) kn-keyword=polymyxin E (PME) en-keyword=NK cells kn-keyword=NK cells en-keyword=IFN-gamma kn-keyword=IFN-gamma END