Ustyuzhanina Nadezhda E, Anisimova Natalia Yu, Bilan Maria I, Donenko Fedor V, Morozevich Galina E, Yashunskiy Dmitriy V, Usov Anatolii I, Siminyan Nara G, Kirgisov Kirill I, Varfolomeeva Svetlana R, Kiselevskiy Mikhail V, Nifantiev Nikolay E
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia.
N.N. Blokhin National Medical Research Center of Oncology, Kashirskoe Shosse 24, 115478 Moscow, Russia.
Pharmaceuticals (Basel). 2021 Oct 24;14(11):1074. doi: 10.3390/ph14111074.
The immunosuppression and inhibition of hematopoiesis are considered to be reasons for the development of complications after intensive chemotherapy and allogeneic hematopoietic stem cell transplantation. Chondroitin sulfate (), isolated from the fish , and fucosylated chondroitin sulfate (), isolated from the sea cucumber , were studied for their roles as stimulators of hematopoiesis in a model of cyclophosphamide-induced immunosuppression in mice. The recombinant protein r G-CSF was applied as a reference. The studied polysaccharides were shown to stimulate the release of white and red blood cells, as well as platelets from bone marrow in immunosuppressed mice, while r G-CSF was only responsible for the significant increase in the level of leucocytes. The analysis of different populations of leucocytes in blood indicated that r G-CSF mainly stimulated the production of neutrophils, whereas in the cases of the studied saccharides, increases in the levels of monocytes, lymphocytes and neutrophils were observed. The normalization of the level of the pro-inflammatory cytokine IL-6 in the serum and the recovery of cell populations in the spleen were observed in immunosuppressed mice following treatment with the polysaccharides. An increase in the proliferative activity of hematopoietic cells CD34(+)CD45(+) was observed following ex vivo polysaccharide exposure. Further study on related oligosaccharides regarding their potential as promising drugs in the complex prophylaxis and therapy of hematopoiesis inhibition after intensive chemotherapy and allogeneic hematopoietic stem cell transplantation seems to be warranted.
免疫抑制和造血抑制被认为是强化化疗和异基因造血干细胞移植后并发症发生的原因。研究了从鱼类中分离得到的硫酸软骨素（）和从海参中分离得到的岩藻糖基化硫酸软骨素（）在环磷酰胺诱导的小鼠免疫抑制模型中作为造血刺激剂的作用。将重组蛋白r G-CSF用作对照。研究表明，所研究的多糖可刺激免疫抑制小鼠骨髓中白细胞、红细胞以及血小板的释放，而r G-CSF仅导致白细胞水平显著升高。对血液中不同白细胞群体的分析表明，r G-CSF主要刺激中性粒细胞的产生，而在所研究的糖类情况下，观察到单核细胞、淋巴细胞和中性粒细胞水平均有所增加。多糖处理后的免疫抑制小鼠血清中促炎细胞因子IL-6水平恢复正常，脾脏中的细胞群体也得以恢复。体外多糖暴露后，造血细胞CD34(+)CD45(+)的增殖活性增加。进一步研究相关寡糖在强化化疗和异基因造血干细胞移植后造血抑制综合预防和治疗中作为有前景药物的潜力似乎是有必要的。
