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阿霉素治疗后小鼠针对同种异体肿瘤细胞的免疫反应发育增强。

Augmentation of the development of immune responses of mice against allogeneic tumor cells after adriamycin treatment.

作者信息

Tomazic V, Ehrke M J, Mihich E

出版信息

Cancer Res. 1981 Sep;41(9 Pt 1):3370-6.

PMID:7260903
Abstract

In C57BL/6J mice, depending on the dose of P815 cells used for immunization, Adriamycin exerted different effects on the cell-mediated lytic response and complement-dependent cytotoxicity. At the dose of 3 X 10(7) P815 cells, Adriamycin treatment had no apparent effect on cell-mediated lytic response regardless of timing of drug treatment. At lower doses of antigen (10(7) or 5 X 10(6) cells), the response was augmented in Adriamycin-pretreated mice. Similarly, under conditions which led to a suboptimal complement-dependent humoral response of untreated control, Adriamycin pretreatment resulted in an augmented response; under conditions of maximal response, Adriamycin was suppressive. Suppression was maximal if the drug was injected at either the same time or shortly before or after antigen. The cell-mediated lytic response was proportional to the dose of antigen used, while the complement-dependent humoral lytic response was inversely proportional to dose of antigen in the range used in these experiments. Secondary cell-mediated lytic response in culture was also augmented if mice had been pretreated with Adriamycin 5 days before the primary immunization. The cell-mediated lytic response of spleen and peritoneal exudate cells from mice immunized with relatively low doses of P815 cells 5 days after treatment with Adriamycin was increased 12 to 15 days after immunization. The cytotoxic effects were present in both plastic adherent and nonadherent fractions of either spleen or peritoneal cell populations. All these effector cells were found to be anti-Thy 1.2 sensitive. The phagocytic activity of spleen cells was increased after immunization, but no drug effect was observed; following 24 hr of culture, however, cells from drug-treated immunized donors had increased phagocytic activity as compared to that of controls. Increased phagocytosis also developed in cells nonadherent to plastic.

摘要

在C57BL/6J小鼠中,根据用于免疫的P815细胞剂量,阿霉素对细胞介导的溶解反应和补体依赖性细胞毒性产生不同影响。在3×10⁷个P815细胞的剂量下,无论药物治疗时间如何,阿霉素治疗对细胞介导的溶解反应均无明显影响。在较低剂量的抗原(10⁷或5×10⁶个细胞)时,阿霉素预处理的小鼠反应增强。同样,在导致未处理对照的补体依赖性体液反应次优的条件下,阿霉素预处理导致反应增强;在最大反应条件下,阿霉素具有抑制作用。如果在抗原同时或之前或之后不久注射药物,抑制作用最大。细胞介导的溶解反应与所用抗原剂量成正比,而补体依赖性体液溶解反应与这些实验中使用的抗原剂量成反比。如果小鼠在初次免疫前5天用阿霉素预处理,培养中的二次细胞介导的溶解反应也会增强。在用阿霉素治疗5天后用相对低剂量的P815细胞免疫的小鼠中,脾脏和腹腔渗出细胞的细胞介导的溶解反应在免疫后12至15天增加。细胞毒性作用存在于脾脏或腹腔细胞群体的塑料贴壁和非贴壁部分。所有这些效应细胞均被发现对抗Thy 1.2敏感。免疫后脾脏细胞的吞噬活性增加,但未观察到药物作用;然而,培养24小时后,与对照相比,来自药物处理的免疫供体的细胞吞噬活性增加。在不贴壁于塑料的细胞中也出现了吞噬作用增强。

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