Institute of Chemical Biology and Fundamental Medicine, SB of the Russian Academy of Sciences, Lavrentiev Ave., 8, 630090 Novosibirsk, Russia.
Faculty of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
Molecules. 2024 Mar 20;29(6):1382. doi: 10.3390/molecules29061382.
The exact mechanisms of MS (multiple sclerosis) evolution are still unknown. However, the development of EAE (experimental autoimmune encephalomyelitis simulating human MS) in C57BL/6 mice occurs due to the violation of bone marrow hematopoietic stem cell differentiation profiles, leading to the production of toxic for human autoantibody splitting MBP (myelin basic protein), MOG (mouse oligodendrocyte glycoprotein), five histones, DNA, and RNA. Here, we first analyzed the changes in the relative phosphatase activity of IgGs from C57BL/6 mice blood over time, corresponding to three stages of EAE: onset, acute, and remission. Antibodies have been shown to catalyze the hydrolysis of -nitrophenyl phosphate at several optimal pH values, mainly in the range of 6.5-7.0 and 8.5-9.5. During the spontaneous development of EAE, the most optimal value is pH 6.5. At 50 days after the birth of mice, the phosphatase activity of IgGs at pH 8.8 is 1.6-fold higher than at pH 6.5. During spontaneous development of EAE from 50 to 100 days, an increase in phosphatase activity is observed at pH 6.5 but a decrease at pH 8.8. After mice were immunized with DNA-histone complex by 20 and 60 days, phosphatase activity increased respectively by 65.3 and 109.5 fold (pH 6.5) and 128.4 and 233.6 fold (pH 8.8). Treatment of mice with MOG at the acute phase of EAE development (20 days) leads to a maximal increase in the phosphatase activity of 117.6 fold (pH 6.5) and 494.7 fold (pH 8.8). The acceleration of EAE development after mice treatment with MOG and DNA-histone complex results in increased production of lymphocytes synthesizing antibodies with phosphatase activity. All data show that IgG phosphatase activity could be essential in EAE pathogenesis.
多发性硬化症（MS）的确切发病机制尚不清楚。然而，C57BL/6 小鼠的实验性自身免疫性脑脊髓炎（EAE）的发展是由于骨髓造血干细胞分化谱的破坏，导致产生对人类自身抗体有 毒性的髓鞘碱性蛋白（MBP）、MOG（小鼠少突胶质细胞糖蛋白）、五种组蛋白、DNA 和 RNA 的分裂。在这里，我们首先分析了 C57BL/6 小鼠血液中 IgG 相对磷酸酶活性随时间的变化，对应 EAE 的三个阶段：发病、急性期和缓解期。抗体已被证明在几个最佳 pH 值下催化对硝基苯磷酸酯的水解，主要在 pH 值 6.5-7.0 和 8.5-9.5 范围内。在 EAE 的自发发展过程中，最适 pH 值为 6.5。在小鼠出生后 50 天，IgG 在 pH 8.8 时的磷酸酶活性比在 pH 6.5 时高 1.6 倍。在 EAE 从 50 天到 100 天的自发发展过程中，在 pH 6.5 时观察到磷酸酶活性增加，但在 pH 8.8 时减少。在第 20 天和第 60 天用 DNA-组蛋白复合物免疫小鼠后，磷酸酶活性分别增加了 65.3 倍和 109.5 倍（pH 6.5）和 128.4 倍和 233.6 倍（pH 8.8）。在 EAE 发展的急性期（第 20 天）用 MOG 治疗小鼠会导致磷酸酶活性最大增加 117.6 倍（pH 6.5）和 494.7 倍（pH 8.8）。用 MOG 和 DNA-组蛋白复合物治疗小鼠后 EAE 发展的加速导致产生具有磷酸酶活性的合成抗体的淋巴细胞增加。所有数据表明，IgG 磷酸酶活性可能是 EAE 发病机制中的关键因素。
