Changes in haematopoietic progenitor colony differentiation and proliferation and the production of different abzymes in EAE mice treated with DNA
Changes in haematopoietic progenitor colony differentiation and proliferation and the production of different abzymes in EAE mice treated with DNA
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DOI：
10.1111/jcmm.13289
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发表时间：
2017-12-01
影响因子：
5.3
通讯作者：
Nevinsky, Georgy A.
中科院分区：
文献类型：
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作者：
Aulova, Kseniya S.;Toporkova, Ludmila B.;Nevinsky, Georgy A.
已知用 MOG(35-55)（用于研究人类多发性硬化症各方面的模型）对易患实验性自身免疫性脑脊髓炎 (EAE) 的 C57BL/6 小鼠进行免疫会导致各种抗体酶的产生。能够有效水解髓磷脂碱性蛋白 (MBP)、MOG 和 DNA 的催化 IgG 的产生与小鼠骨髓造血干细胞 (HSC) 的分化特征和增殖水平的变化有关。由于 MOG 模拟具有高 DNase 活性的抗体酶的产生，因此我们比较了 DNA 和 MOG 免疫对 EAE 易感小鼠的影响。与 MOG 相比，DNA 免疫会抑制蛋白尿，降低 MOG 和 DNA 抗体的浓度，并减少抗体酶的产生。 DNA 免疫仅导致 DNase 活性在 40 天内显着增加，比免疫前高 122 倍，与 MOG 处理后获得的最大活性相比高五倍。 DNA和MOG免疫对小鼠骨髓和其他器官中HSC的分化特征、淋巴细胞增殖以及细胞凋亡水平有不同的影响。数据表明，对于C57BL/6小鼠，DNA可能对MOG免疫具有拮抗作用。 C57BL/6 小鼠注射 MOG 后通常快速的免疫反应在 DNA 免疫后明显延迟，这可能是由于 DNA 反应后免疫系统的重新排列所致。
Immunization of experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice with MOG(35-55) (a model used to study aspects of human multiple sclerosis) is known to lead to the production of various abzymes. The production of catalytic IgGs that can efficiently hydrolyse myelin basic protein (MBP), MOG and DNA is associated with changes in the profile of differentiation and level of proliferation of mice bone marrow haematopoietic stem cells (HSCs). As MOG simulates the production of abzymes with high DNase activity, we compared the effects of DNA and MOG immunization on EAE-prone mice. In contrast to MOG, immunization with DNA leads to a suppression of proteinuria, a decrease in the concentrations of antibodies to MOG and DNA and a reduction in abzyme production. Immunization with DNA only resulted in a significant increase in DNase activity over 40 days where it became 122-fold higher than before immunization, and fivefold higher when comparing to the maximal activity obtained after MOG treatment. DNA and MOG immunization had different effects on the differentiation profiles of HSCs, lymphocyte proliferation, and the level of apoptosis in bone marrow and other organs of mice. The data indicate that for C57BL/6 mice, DNA may have antagonistic effects with respect to MOG immunization. The usually fast immune response following MOG injection in C57BL/6 mice is strongly delayed after immunization with DNA, which is probably due to a rearrangement of the immune system following the response to DNA.