Clodronate-liposomes aggravate irradiation-induced myelosuppression by promoting myeloid differentiation,International Journal of Radiation Biology

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Clodronate-liposomes aggravate irradiation-induced myelosuppression by promoting myeloid differentiation
International Journal of Radiation Biology ( IF 2.1 ) Pub Date : 2021-01-11 , DOI: 10.1080/09553002.2021.1857452
Wen Ju _{1,

2,

3} , Wenyi Lu _{1,

2,

3} , Yurong Bao _{1,

2,

3} , Tiantian Sun _{1,

3,

4} , Seyram Yao Adzraku _{2,

3} , Chunling Fu _{1,

2,

3} , Kunming Qi _{1,

2,

3} , Xi Zhang ₅ , Zhenyu Li ₃ , Kailin Xu _{1,

2,

3} , Jianlin Qiao _{1,

2,

3} , Lingyu Zeng _{1,

2,

3}

Affiliation

Abstract

Purpose

Clodronate-liposomes (Clod-Lip) is an effective candidate drug for treating chronic myelomonocytic leukemia, autoimmune hemolytic anemia and immune thrombocytopenic purpura in mice experiments. But its role in hematopoietic recovery after acute myelosuppression is still unknown. We aim to explore the function and underlining mechanisms of Clod-Lip on hematopoietic reconstitution after sublethal dose irradiation in mice.

Materials and methods

Mice at 8-10 weeks received a total-body sublethal dose γ-irradiation (TBI) and injected with Clod-Lip or PBS-Liposomes (PBS-Lip) every 4 days after TBI. The survival rate of each group was recorded. Flow cytometry was used to analyze changes in hematopoietic stem cells and their progenies in bone marrow. ELISA and RT-qPCR were used for the analysis of hematopoietic regulatory factors. Regarding IL-1β inhibition, 25 mg/kg diacerein or an equal volume of DMSO was intraperitoneally injected into mice every day after TBI.

Results

In sublethal dose-irradiated mice, Clod-Lip reduced the survival rate, the total number of bone marrow and hematopoietic stem cells, delayed peripheral blood recovery of red blood cells and platelets. However, it could increase the number of CMP, MEP and myeloid cells, which suggested that Clod-Lip could induce HSC to myeloid differentiation in vivo. We further verified that Clod-Lip may induce myeloid differentiation by bone marrow microenvironmental factor IL-1β.

Conclusions

In summary, this study suggested that Clod-Lip may aggravate inhibitor effect of hematopoietic function and promote myeloid differentiation in myelosuppression mice model.

中文翻译：

氯膦酸盐脂质体通过促进骨髓分化加重辐射诱导的骨髓抑制

摘要

目的

Clodronate-liposomes（Clod-Lip）是小鼠实验中治疗慢性粒单核细胞白血病、自身免疫性溶血性贫血和免疫性血小板减少性紫癜的有效候选药物。但其在急性骨髓抑制后造血功能恢复中的作用尚不清楚。我们的目的是探索Clod-Lip对小鼠亚致死剂量照射后造血重建的作用和机制。

材料和方法

8-10 周的小鼠接受全身亚致死剂量的 γ 辐射 (TBI)，并在 TBI 后每 4 天注射一次 Clod-Lip 或 PBS-脂质体 (PBS-Lip)。记录每组的存活率。流式细胞术用于分析骨髓中造血干细胞及其后代的变化。ELISA 和 RT-qPCR 用于分析造血调节因子。关于 IL-1β 抑制，TBI 后每天将 25 mg/kg 双醋瑞因或等体积的 DMSO 腹腔注射到小鼠体内。