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p185抗体可致小鼠流产的研究

李晓华 秦慧莲 Mery L Disis 何球藻

  【摘要】 目的 通过体内实验进一步验证p185蛋白的免疫原性,旨在研究该蛋白作为肿瘤疫苗的可能性。方法 用Sephadex G200层析柱分离的p185蛋白组分与佐剂混合免疫BALB/c小鼠,经ELISA验证血清中出现p185抗体后与健康的同品系雄性鼠交配,以阴栓形成提示交配成功,观察雌鼠产仔率,子宫形态及免疫病理。结果 免疫鼠产仔率明显低于仅用佐剂免疫的对照组(P<0.05),子宫内发现胚胎坏死,病检显示子宫组织有弥散性中性粒细胞浸润和局灶性坏死,并有免疫复合物沉积,提示p185免疫能诱导小鼠流产。结论 这一实验结果从体内进一步证实p185的免疫原性。为该蛋白作为肿瘤疫苗提供实验资料,同时该模型可用于对胚胎性肿瘤抗原的免疫原性研究。
  【主题词】 p185蛋白 流产 肿瘤胚胎抗原 抗原,肿瘤

Study on miscarriage of mice immunized with p185 Li Xiaohua*,Qon Huilian,Mery L Disis,et al. * Department of Immunology,Shanghai Medical University,Shanghai 200032
  【Abstract】 Objective To identify the immunogenicity of p185 onco-protein in vivo and to study its possibility as a tumor vaccine. Methods p185 HER2/neu onco-protein crude products,derived from 3T3-neu transfected cell lysates by Sephadex G200 chromatography column,were used with adjuvant to ip immunize female BALB/c mice.When 185 antibody positive the mice were mated with males.Successful mating was evidenced by the presence of vaginal embolus. Results The average of the offspring per delivery from immunized mice was significantly lower than that from the control mice immunized with adjuvant alone.The pathological findings revealed that there were diffused infiltration of neu-trophiles,focal necroses as well as immunocomplex deposits on the wall of uterus resulting in necrotic fetuses.These indicated that the pregnant mice which had been immunized with p185. Conclusions Above results suggest the p185 onco-protein are the tumor antigen and can induce the immune response in BALB/c mice.This model may be useful for studying the immunogenicity of the fetal tumor antigen.
  【Subject words】 p185 onco-protein Abortion Fetal tumor antigen Antigen,neoplasm

  原癌基因HER2/neu编码的分子量为185000跨膜糖蛋白,属于生长因子类受体家族,它具有PTK激酶活性〔1〕。该蛋白在哺乳类的胎盘及胚胎器官组织表达较高〔2,3〕,且在不同种属间有较高的同源性〔4〕。人类肿瘤细胞p185产物表达量的升高与肿瘤的发展及不良预后密切相关〔5,6〕。已有实验资料提示,p185在恶性肿瘤细胞上的高表达使它有可能作为肿瘤免疫治疗的靶抗原。我们曾报道,用表达p185的3T3-neu转基因细胞的膜裂解

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