Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane.
Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane.
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DOI：
10.1084/jem.180.6.2341
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发表时间：
1994-12-01
期刊：
影响因子：
--
通讯作者：
Reeves WH
中科院分区：
文献类型：
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作者：
Satoh M;Reeves WH
腹腔内注射降植烷（2,6,10,14 - 四甲基十五烷）是获取富含单克隆抗体的腹水的一种标准技术。然而，降植烷也会在BALB/c小鼠中诱发浆细胞瘤以及一种类似类风湿性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。我们在此报道，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）特征性的自身抗体。在单次注射0.5毫升降植烷后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只相同年龄和性别的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征性的自身抗体。降植烷诱导与SLE相关的自身抗体可能有助于理解细胞因子异常产生在自身抗体产生以及自身免疫性疾病发病机制中的作用。此外，降植烷诱导高滴度自身抗体这一情况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会与注射的杂交瘤所分泌的单克隆抗体共同纯化。
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.