THE ROLE OF OIL AND AGALACTOSYL IGG IN THE INDUCTION OF ARTHRITIS IN RODENT MODELS
THE ROLE OF OIL AND AGALACTOSYL IGG IN THE INDUCTION OF ARTHRITIS IN RODENT MODELS
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DOI：
10.1002/eji.1830210425
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发表时间：
1991-04-01
影响因子：
5.4
通讯作者：
RADEMACHER, T
中科院分区：
文献类型：
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作者：
ROOK, G;THOMPSON, S;RADEMACHER, T
无半乳糖基IgG [Gal（O）]的比例在人类风湿性关节炎和结核病中升高。 我们在此报告，在第0天和第50天将降植烷注射到小鼠腹腔中，这是已知的诱导浆细胞瘤和关节炎，也诱导了Gal（O）比例的上升，与结合牛分枝杆菌65 kDa热休克蛋白（hsp 65）的IgG抗体水平的同时上升相关。 Gal（O）百分比最高的CBA/Igb小鼠中有一定比例发生关节炎。 用50 μ g重组分枝杆菌hsp 65腹膜内（i. p.）在第-10天，或在第-2天在两次注射降植烷的第一次之前用500拉德照射，将关节炎的发病率从对照动物的24%分别降低到5.3%和0.4%。 疾病发生率的降低与50-75天的%Gal（O）的较小升高相关，尽管150-200天的水平不受影响。油的致关节炎作用不限于降植烷模型，因为在用II型胶原免疫DBA/1小鼠之前21天单次腹膜内注射油减少了这种关节炎发作的平均天数，[我们之前已经表明与升高的%Gal（O）相关]，从38天到15天（p < 0.001）。 一种解释是，当Gal（O）%升高时，自身免疫原性刺激更可能诱发疾病。由于已知油肉芽肿分泌白细胞介素6，其具有B细胞调节特性，由类风湿性滑膜细胞分泌，我们检测了白细胞介素6转基因小鼠的血清，发现Gal（O）的百分比显著升高。 因此，我们认为，油在诱导关节炎中的作用是细胞因子释放的失调，其中Gal（O）百分比的升高可能是直接或间接的后果，与对自身免疫原性刺激的易感性增加有关。
The proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65-kDa heat-shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50-mu-g of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day -10, or with 500 rad irradiation on day -2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the %Gal(O) at 50-75 days, although levels at 150-200 days were not affected.The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised %Gal(O)], from 38 to 15 days (p < 0.001). One interpretation is that an autoimmunogenic stimulus, given when %Gal(O) is raised, is more likely to evoke disease.Since oil granulomata are known to secrete interleukin 6, which has B cell-regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6-transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.