Misawa E, Sakurai T, Yamada M, Hayasawa H, Motoyoshi K
Biochemical Research Laboratory, Morinaga Milk Industry Co. Ltd., Higashihara 5-1-83, 228-8583, Zama, Kanagawa, Japan.
Int J Immunopharmacol. 2000 Nov;22(11):967-77. doi: 10.1016/s0192-0561(00)00061-8.
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.
我们研究了巨噬细胞集落刺激因子（M-CSF）和白细胞介素-2（IL-2）对体内外NK1.1(+)细胞活性的影响。给予M-CSF可增加脾脏NK1.1(+)细胞的数量（与生理盐水组相比：P<0.01）。此外，与单一治疗相比，M-CSF和IL-2联合使用（M-CSF+IL-2）使NK1.1(+)细胞数量产生协同性增加（与生理盐水组相比：P<0.001）。从各治疗组小鼠（四个治疗组：生理盐水组、单独使用IL-2组、单独使用M-CSF组、M-CSF+IL-2组）的脾脏中分离出NK1.1(+)细胞，并在体外评估其功能（IL-2诱导的增殖、γ干扰素产生及细胞抑制活性）。与生理盐水组和单独使用IL-2组的细胞相比，单独使用M-CSF组和M-CSF+IL-2组处理的小鼠的NK1.1(+)细胞在IL-2诱导的增殖、γ干扰素产生及细胞抑制活性方面表现出更高的反应性。通过“肺部清除试验”（肺部Yac-1细胞的清除情况）评估，给予M-CSF和IL-2可增强体内NK活性。并且M-CSF+IL-2治疗诱导的NK活性在四种治疗中最高。为了显示给予M-CSF和IL-2上调体内NK活性的实际效果，研究了四种治疗对实验性肿瘤转移模型的影响。单独使用IL-2、单独使用M-CSF和M-CSF+IL-2治疗均减少了B16黑色素瘤的转移。并且M-CSF+IL-2治疗在抗转移活性方面比单一治疗更具优势。我们的结果表明，给予M-CSF可增加对IL-2具有良好反应性的NK1.1(+)细胞数量。此外，体内M-CSF和IL-2联合治疗可增强NK1.1(+)细胞的增加。并且这些作用有助于体内的抗转移活性。
