Effects of macrophage-colony-stimulating factor on cyclophosphamide-injected mouse NK1.1+ cell activity |
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Authors: | Takuma Sakurai Eriko Misawa Muneo Yamada Hirotoshi Hayasawa Kazuo Motoyoshi |
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Institution: | (1) Biochemical Research Laboratory, Morinaga Milk Industry Co. Ltd., No. 1-83, 5-Chome Higashihara Zama City, Kanagawa pref. 228, Japan Tel.: +81-0462-52-3070; Fax: +81-0462-52-3075, JP;(2) Third Department of Internal Medicine, National Defense Medical College, Japan, JP |
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Abstract: | 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 γ 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.
Received: 28 September 1999 / Accepted: 23 December 1999 |
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Keywords: | M-CSF Cyclophosphamide NK1 1 Metastasis |
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