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药物标记抗体体外导向治疗系统性红斑狼疮所致血小板减少

姜振宇,于黎黎,曹梦园,姚 程*   

  1. 吉林大学第一医院血液肿瘤科,吉林 长春130021
  • 收稿日期:2005-03-08 修回日期:1900-01-01 出版日期:2006-07-28 发布日期:2006-07-28
  • 通讯作者: 姚 程

Targeting therapy of SLE associated thrombocytopeniawith labeled antibody in vitro

JIANG Zhen-yu, YU Li-li,CAO Meng-yuan,YAO Cheng*   

  1. Department of Hematology and Oncology, First Hospital,Jilin University, Changchun 130021, China
  • Received:2005-03-08 Revised:1900-01-01 Online:2006-07-28 Published:2006-07-28
  • Contact: YAO Cheng

摘要: 目的:探讨药物标记抗体导向治疗系统性红斑狼疮(SLE)所致血小板减少的可行性及效果。 方法:将静脉注射用免疫球蛋白(IVIG)与免疫抑制剂MTX交联制备成直接和间接标记抗体,使之对单核-巨噬细胞产生特异的杀伤作用,用免疫荧光法检测Fc段结合活性,以Fc受体阳性的小鼠巨噬细胞和人单核细胞白血病U937为靶细胞,用MTT法检测标记前后MTX杀伤活性及标记抗体的特异性杀伤活性。 结果:标记抗体的杀伤活性明显大于游离MTX,标记抗体对Fc受体阳性的U937细胞的杀伤活性明显大于Fc受体阴性细胞,标记抗体能抑制巨噬细胞的吞噬功能,间接标记抗体IVIG-HSA-MTX杀伤活性明显大于直接标记抗体IVIG-MTX。 结论:标记抗体在体外对单核、巨噬细胞显示了相对特异的杀伤活性。

关键词: 受体, Fc, 免疫球蛋白, 静脉内, 红斑狼疮 , 系统性, 血小板减少

Abstract: Objective To discuss the feasibility and effect of labeled antibody on targeting therapy of systemic lupus erythematosus (SLE) associated thrombocytopenia. Methods MTX-IVIG conjugate was prepared by indirect and direct cross linking,and the binding ability of it to Fc fragment was detected by indirect immunofluor-escence.The killing activity of the conjugate was detected by MTT method using murine macrophage with Fc receptor and strain U937 of human monocytic leukemia cell as targets. Results Conjugation showed stronger cytotoxicity upon target cells than free MTX,and it showed less cytotoxic effect on Fc receptor negative cells compared with the positive ones. IVIG-HSA-MTX restrained the phagocyte of macrophage. The killing effect of IVIG-HSA-MTX was significantly stronger than that of IVIG-MTX. Conclusion The conjugation can show a highly specific cytotoxicity upon mononuclear-macrophage in vitro.

Key words: receptor, Fc, immunoglobulins, intravenous, lupus erythematosus, systemic, thrombocytopenia

中图分类号: 

  • R558.2