title: Effects of macrophage colony-stimulating factor and interleukin-2 administration on NK1.1(+) cells in mice.
abstract: We studied the effects of M-CSF and IL-2 on NK1.1(+) cell activity in vivo and in vitro. Administration of M-CSF increased the number of splenic NK1.1(+) cells (vs. saline: P<0.01). Moreover, the combination of M-CSF and IL-2 (M-CSF+IL-2) produced a synergistic expansion of the number of NK1.1(+) cells compared with each single treatment (vs. saline: P<0.001). The NK1.1(+) cells were isolated from the spleen of each treated mouse (four treatment groups: saline, IL-2 alone, M-CSF alone, M-CSF+IL-2) and their functions (IL-2-induced proliferation, IFN-gamma production and cytostatic activity) were evaluated in vitro. The NK1.1(+) cells from M-CSF alone and M-CSF+IL-2 treated mice showed greater responsiveness in terms of IL-2-induced proliferation, production of IFN-gamma and cytostatic activity than the cells from saline and IL-2 alone treated mice. The NK activity in vivo was enhanced by the administration of M-CSF and IL-2, as assessed by the 'Lung clearance assay' (clearance of Yac-1 cells in lung). And the M-CSF+IL-2 treatment induced the highest NK activity of the four treatments. To show a practical effect of upregulation of NK activity in vivo by M-CSF and IL-2 administration, the effect of the four treatments on an experimental tumor metastasis model was examined. The IL-2 alone, M-CSF alone and M-CSF+IL-2 treatment reduced the metastasis of B16 melanoma. And the M-CSF+IL-2 treatment proved of greater benefit to the antimetastatic activity than each single treatment. Our results demonstrated that the administration of M-CSF increases the number of NK1.1(+) cells, which have good responsiveness to IL-2. Furthermore, the combination treatment of M-CSF and IL-2 in vivo augments the increase of NK1.1(+) cells. And these effects can contribute to the antimetastatic activity in vivo.
authors.affiliation: Biochemical Research Laboratory, Morinaga Milk Industry Co. Ltd., Higashihara 5-1-83, 228-8583, Zama, Kanagawa, Japan. e_misawa@morinagamilk.co.jp
authors.forename: E
authors.initials: E
authors.lastname: Misawa
authors.forename: T
authors.initials: T
authors.lastname: Sakurai
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Hayasawa
authors.forename: K
authors.initials: K
authors.lastname: Motoyoshi
mesh_terms: D000818:Animals; D000941:Antigens / Q000032:analysis*; D000950:Antigens, Ly; D000954:Antigens, Surface; D016466:CHO Cells; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D008546:Melanoma, Experimental / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000032:analysis*
chemical_list: D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D007376:Interleukin-2; C527203:KLRB1 protein, human; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma