Booster effect of interleukin-2 on natural killer 1.1+ cells stimulated by administration of macrophage colony-stimulating factor in mice.
The authors studied the combined effects of macrophage colony-stimulating factor (M-CSF) and interleukin (IL)-2 on the functions and antitumor activity of natural killer (NK) 1.1+ cells in vitro and in vivo. NK1.1+ cells were isolated from the spleen of mice treated with saline or M-CSF, and their functions (proliferation, production of IFN-gamma, and cytotoxicity) evaluated in vitro. Although the proliferation of and production by NK1.1+ cells was stimulated by the addition of IL-2, the cells from the M-CSF-treated mice responded better. Furthermore, the cytotoxicity against Yac-1 cells and B16 melanoma cells was stimulated by M-CSF administration and enhanced by the addition of IL-2 and IL-12. These results demonstrated that M-CSF treatment augmented the functions of NK1.1 cells, and IL-2 and IL-12 boosted these activities in vitro. The authors then examined the effects of co-administration of M-CSF and IL-2 in vivo. The clearance of B16 cells in lung was augmented by the administration of M-CSF but not IL-2. However, M-CSF + IL-2 treatment further enhanced the clearance activity. The anti-metastatic activity was also enhanced by the M-CSF + IL-2 treatment. Furthermore, the survival of B16-bearing mice was prolonged by M-CSF + IL-2. These results suggested that administration of IL-2 boosts the functions of NK1.1+ cells, which are augmented preliminarily by the administration of M-CSF.
Misawa
Eriko
E
Biochemical Research Laboratory, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa, Japan. e_misawa@morinagamilk.co.jp
Sakurai
Takuma
T
Yamada
Muneo
M
Hayasawa
Hirotoshi
H
Motoyoshi
Kazuo
K
D000818:Animals; D000941:Antigens / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface; D002455:Cell Division / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D007371:Interferon-gamma / Q000032:analysis / 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*; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000276:immunology; D011897:Random Allocation; D012680:Sensitivity and Specificity
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D007376:Interleukin-2; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma