RRC ID 43273
Author Zhong M, Kadota Y, Shimizu Y, Gohda E.
Title Induction of cytolytic activity and interferon-gamma production in murine natural killer cells by polymyxins B and E.
Journal Int Immunopharmacol
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 lack 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 polymyxin 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 mug/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-alpha 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.
Volume 8(3)
Pages 508-13
Published 2008-3-1
DOI 10.1016/j.intimp.2007.11.001
PII S1567-5769(07)00356-6
PMID 18279806
MeSH Animals Anti-Bacterial Agents / pharmacology* Colistin / pharmacology* Cytotoxicity, Immunologic / drug effects* Female Interferon-gamma / biosynthesis* Killer Cells, Natural / drug effects* Killer Cells, Natural / immunology Mice Mice, Inbred C57BL Polymyxin B / pharmacology*
IF 3.943
Times Cited 9
WOS Category PHARMACOLOGY & PHARMACY IMMUNOLOGY
Resource
Human and Animal Cells