Effects of macrophage-colony-stimulating factor on cyclophosphamide-injected mouse NK1.1+ cell activity.
We injected cyclophosphamide into mice and examined their natural killer (NK) activity both in vitro and in vivo. Cyclophosphamide injection temporarily abrogated the lung clearance activity of Yac-1 lymphoma cells, which is considered to be an index of NK activity in vivo. However, administration of recombinant human macrophage-colony-stimulating-factor (rhM-CSF) to cyclophosphamide-injected mice restored the lung clearance activity. To clarify whether the administration of rhM-CSF activated NK cells, we purified NK1.1+ cells from mice treated with cyclophosphamide and/or rhM-CSF and examined their functions (cytotoxicity, proliferation, and interferon gamma production) in vitro. Cyclophosphamide injection decreased the number, but did not suppress the functions of NK1.1+ cells. The numbers of NK1.1+ cells in cyclophosphamide-injected mice restored by rhM-CSF administration. And the functions of NK1.1+ cells from both saline-injected and cyclophosphamide-injected mice were accelerated by rhM-CSF administration. These results suggested that the temporary abrogation of NK activity in vivo caused by cyclophosphamide injection was due to a decrease in the number and not to suppression of the functions of NK1.1+ cells. The injection of cyclophosphamide into mice increased the number of tumor (B16 melanoma) nodules formed in the lungs and liver. However, treatment with rhM-CSF recovered the anti-metastatic activity in the lungs of cyclophosphamide-injected mice. These results show that administration of rhM-CSF restores NK activity suppressed by cyclophosphamide injection in vivo.
Sakurai
T
T
Biochemical Research Laboratory, Morinaga Milk Industry Co. Ltd., Zama City, Kanagawa pref., Japan.
Misawa
E
E
Yamada
M
M
Hayasawa
H
H
Motoyoshi
K
K
D000818:Animals; D000941:Antigens / Q000032:analysis*; D000950:Antigens, Ly; D000954:Antigens, Surface; D003520:Cyclophosphamide / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects*; D037181:Lectins, C-Type; D008175:Lung Neoplasms / Q000556:secondary; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; C527203:KLRB1 protein, human; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D003520:Cyclophosphamide