小鼠对IFN-α1转染的Friend白血病细胞的局部和全身反应

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3C18系Frienol白血病细胞(FLC)对小鼠IFN-α/β具有完全的抵抗性,经IFN-αl基因转染后此抵抗性仍存在,且能分泌高剂量的IFN,接种小鼠后能出现持续数周的干扰素血症,故作者选用此细胞建立模型,观察接种IFN-αl基因转染FLC后小鼠的局部和全身反应,以进一步了解宿主抑制此肿瘤生长的机制。 应用逆转录病毒将IFN-αl基因转入FLC,选出克隆IFN-αlCl-11FLC,可向培养液中分泌IFN-αl256~512U/ml,对照转染的FLC(TC-2)不分泌IFN。具有免疫活性的DBA2+/bg小鼠皮下注射TC-2 FLC后可生成快速生长的肿瘤,接种后20~35天后肿瘤呈现大面积坏死,小鼠存活时间和存活数量较对照组显著增多。IFN-αl C1-11 FLC接种缺失NK细胞活性的bg/bg小鼠后呈现相似的致瘤性下降现象,用单抗去除DBA/2小鼠体内的CD4~+CD8~+细胞或粒细胞并不影响实验组小鼠的肿瘤生长曲线、肿瘤发生率及存活时间;经一系列处理后获得完全性免疫抑制的SIA裸鼠用于实验,实验组小鼠肿瘤与对照组TC-2肿瘤生长曲线仅稍有差异,并不显著,二者在存活时间、存活数量上并无差异。光镜检查发现在第7、14天,接种TC-2细胞小鼠肿瘤在皮肤表面破溃,在肿瘤边缘仅见少量巨噬细胞和中性粒细胞;在接利IFN-αl C1-11细胞小鼠,肿瘤仍在网状胶原层,有广泛的细胞坏死和凋亡,肿 3C18 Frienol leukemia cells (FLC) are completely resistant to mouse IFN-α/β. After transfection with IFN-α1, this resistance still exists, and can secrete high doses of IFN. For several weeks of interferonemia, the authors used this cell model to observe the local and systemic responses of the mice infected with IFN-α1 gene transfected with FLC to further understand the host’s mechanism of suppressing this tumor growth. The IFN-α1 gene was transfected into FLC by retrovirus. Clone IFN-αlCl-11FLC was selected and IFN-α could be secreted into the culture medium from 256 to 512 U/ml. The control transfected FLC (TC-2) did not secrete IFN. Immunostimulating DBA2+/bg mice injected subcutaneously with TC-2 FLC can generate rapidly growing tumors. After 20 to 35 days of inoculation, the tumors showed extensive necrosis. The survival time and the number of surviving mice were significantly increased compared with the control group. IFN-αl C1-11 FLC showed a similar reduction in tumorigenicity after inoculation of bg/bg mice lacking NK cell activity, and the CD4 + CD8 + cells or granulocytes in DBA/2 mice were removed with a monoclonal antibody. Does not affect the tumor growth curve, tumor incidence and survival time of mice in the experimental group; SIA nude mice with complete immunosuppression after a series of treatments are used in the experiments, the growth curve of TC-2 tumors in the experimental group and the control group. Only slightly different, not significant, there is no difference in the survival time, the number of survival. Light microscopy revealed that on day 7 and 14, tumors of mice inoculated with TC-2 cells ruptured on the surface of the skin, and only a few macrophages and neutrophils were seen at the edge of the tumor; the cells were positive for IFN-αl C1-11 cells. Rats, the tumor is still in the reticular collagen layer, with extensive cell necrosis and apoptosis, swollen
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