Sparwasser T, Hültner L, Koch E S, Luz A, Lipford G B, Wagner H
Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Germany.
J Immunol. 1999 Feb 15;162(4):2368-74.
Bacterial DNA and the synthetic CpG-oligodeoxynucleotides (ODNs) derived thereof have attracted attention because they activate cells of the adaptive immune system (lymphocytes) and the innate immune system (APCs) in a sequence-dependent manner. Here, we addressed whether CpG-ODNs affect hemopoiesis. Challenging mice with immunostimulatory CpG-ODN sequences led to transient splenomegaly, with a maximum increase of spleen weight at day 6. The induction of splenomegaly by CpG-ODNs was sequence-specific, dose-dependent, and associated with an increase in splenic cell count, in numbers of granulocyte-macrophage CFUs (GM-CFUs), and early erythroid progenitors (burst-forming units-erythroid). The transfer of spleen cells from CpG-ODN-pretreated animals into lethally irradiated syngeneic mice yielded an increase of spleen CFUs. Furthermore, the challenge of sublethally irradiated mice with CpG-ODNs caused radioprotective effects, in that recovery of GM-CFUs and cytotoxic T cell function was enhanced. The increase in GM-CFU and CTL function correlated with an enhanced resistance to Listeria infection in irradiated mice. We conclude from these data that CpG-ODNs trigger extramedullary hemopoiesis, and that this finding could be of therapeutic relevance in myelosuppression.
细菌DNA及其衍生的合成CpG寡脱氧核苷酸（ODN）已引起关注，因为它们以序列依赖性方式激活适应性免疫系统（淋巴细胞）和先天性免疫系统（抗原呈递细胞）的细胞。在此，我们探讨了CpG-ODN是否影响造血作用。用免疫刺激性CpG-ODN序列攻击小鼠会导致短暂性脾肿大，在第6天脾脏重量增加最多。CpG-ODN诱导的脾肿大具有序列特异性、剂量依赖性，并且与脾细胞计数增加、粒细胞-巨噬细胞集落形成单位（GM-CFU）数量增加以及早期红系祖细胞（红系爆式形成单位）数量增加有关。将来自CpG-ODN预处理动物的脾细胞转移到经致死性照射的同基因小鼠中，会使脾集落形成单位增加。此外，用CpG-ODN攻击经亚致死性照射的小鼠会产生辐射防护作用，因为GM-CFU和细胞毒性T细胞功能的恢复得到增强。GM-CFU和CTL功能的增加与照射小鼠对李斯特菌感染的抵抗力增强相关。我们从这些数据得出结论，CpG-ODN触发髓外造血作用，并且这一发现可能在骨髓抑制方面具有治疗意义。
