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通过腹腔注射 pristane 在 BALB/c 小鼠中诱导狼疮相关自身抗体。

Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane.

作者信息

Satoh M, Reeves W H

机构信息

Department of Medicine and Microbiology/Immunology, Thurston Arthritis Research Center, Chapel Hill, North Carolina.

出版信息

J Exp Med. 1994 Dec 1;180(6):2341-6. doi: 10.1084/jem.180.6.2341.

Abstract

Intraperitoneal injection of pristane (2,6,10,14 tetramethylpentadecane) is a standard technique for obtaining monoclonal antibody-enriched ascitic fluid. However, pristane also induces plasmacytomas and an erosive arthritis resembling rheumatoid arthritis in BALB/c mice, probably as a consequence of enhanced interleukin 6 production. We report here that the production of autoantibodies characteristic of systemic lupus erythematosus (SLE) is a further consequence of injecting pristane in BALB/c mice. Anti-Su antibodies appeared as early as 1-2 mo after a single injection of 0.5 ml pristane, followed by anti-U1RNP and anti-Sm antibodies after 2-4 mo. Within 6 mo of pristane injection, 9 of 11 BALB/c mice had developed anti-Su, anti-U1RNP, anti-U2RNP, anti-Sm, and possibly anti-U5RNP antibodies. Autoantibodies were not produced by 20 BALB/c mice of the same age and sex that were not injected with pristane. Thus, autoantibodies characteristic of lupus were induced in mice that are not usually considered to be genetically susceptible to the disease. The induction of autoantibodies associated with SLE by pristane may be relevant to understanding the role of abnormal cytokine production in autoantibody production and the pathogenesis of autoimmune disease. Furthermore, the induction of high titer autoantibodies by pristane dictates caution in the use of ascitic fluid as a source of monoclonal antibodies, since the polyclonal antibodies induced by pristane may copurify with the monoclonal antibody secreted by an injected hybridoma.

摘要

腹腔注射降植烷(2,6,10,14-四甲基十五烷)是获取富含单克隆抗体腹水的标准技术。然而,降植烷还会在BALB/c小鼠中诱发浆细胞瘤以及类似类风湿关节炎的侵蚀性关节炎,这可能是白细胞介素6产生增加的结果。我们在此报告,在BALB/c小鼠中注射降植烷的另一个后果是产生系统性红斑狼疮(SLE)特有的自身抗体。单次注射0.5 ml降植烷后1 - 2个月就出现了抗-Su抗体,2 - 4个月后出现抗-U1RNP和抗-Sm抗体。在注射降植烷的6个月内,11只BALB/c小鼠中有9只产生了抗-Su、抗-U1RNP、抗-U2RNP、抗-Sm以及可能的抗-U5RNP抗体。未注射降植烷的20只同龄同性别BALB/c小鼠未产生自身抗体。因此,在通常不被认为对该疾病具有遗传易感性的小鼠中诱导出了狼疮特有的自身抗体。降植烷诱导与SLE相关的自身抗体可能与理解细胞因子产生异常在自身抗体产生和自身免疫性疾病发病机制中的作用有关。此外,降植烷诱导产生高滴度自身抗体提示在使用腹水作为单克隆抗体来源时要谨慎,因为降植烷诱导的多克隆抗体可能与注射的杂交瘤分泌的单克隆抗体一起纯化。

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