Granulocyte colony-stimulating factor (G-CSF) is used in clinical practice to mobilize cells from the bone marrow to the blood; however, it is not always effective. We show that cobalt protoporphyrin IX (CoPP) increases plasma concentrations of G-CSF, IL-6, and MCP-1 in mice, triggering the mobilization of granulocytes and hematopoietic stem and progenitor cells (HSPC). Compared with recombinant G-CSF, CoPP mobilizes higher number of HSPC and mature granulocytes. In contrast to G-CSF, CoPP does not increase the number of circulating T cells. Transplantation of CoPP-mobilized peripheral blood mononuclear cells (PBMC) results in higher chimerism and faster hematopoietic reconstitution than transplantation of PBMC mobilized by G-CSF. Although CoPP is used to activate Nrf2/HO-1 axis, the observed effects are Nrf2/HO-1 independent. Concluding, CoPP increases expression of mobilization-related cytokines and has superior mobilizing efficiency compared with recombinant G-CSF. This observation could lead to the development of new strategies for the treatment of neutropenia and HSPC transplantation.

中文翻译：

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钴原卟啉IX增加内源性G-CSF并动员HSC和粒细胞进入血液。

粒细胞集落刺激因子（G-CSF）在临床实践中用于将细胞从骨髓动员到血液中。但是，它并不总是有效的。我们显示钴原卟啉IX（CoPP）增加了小鼠中G-CSF，IL-6和MCP-1的血浆浓度，从而触发了粒细胞和造血干细胞和祖细胞（HSPC）的动员。与重组G-CSF相比，CoPP可动员更多数量的HSPC和成熟的粒细胞。与G-CSF相比，CoPP不会增加循环T细胞的数量。与G-CSF动员的PBMC移植相比，CoPP动员的外周血单个核细胞（PBMC）的移植导致更高的嵌合率和更快的造血重建。尽管CoPP用于激活Nrf2 / HO-1轴，但观察到的效果与Nrf2 / HO-1无关。最后，与重组G-CSF相比，CoPP可提高动员相关细胞因子的表达，并具有出色的动员效率。该观察结果可能导致开发新的策略来治疗中性粒细胞减少和HSPC移植。