Cobalt protoporphyrin IX increases endogenous G‐ CSF and mobilizes HSC and granulocytes to the blood

• DOI: 10.15252/emmm.201809571
• Publication Date: 2019-11-11T08:20:48Z
• Authors: Agata Szade; Krzysztof Szade; Witold N Nowak; Karolina Bukowska...; Lucie Muchova; Monika Gońka; Monika Żukowska; Maciej Cieśla; Neli Kachamakova‐...; Marzena Rams‐Baron; Alicja Ratuszna; Józef Dulak; Alicja Józkowicz
• Keywords: Male; 0301 basic medicine; Medicine (General); hematopoietic stem and progenitor cells; HO‐1; Hematopoietic stem and progenitor cells; HO-1; 610; Protoporphyrins; Mobilization; QH426-470; Granulocyte colony-stimulating factor; granulocyte colony‐stimulating factor; Mice; 03 medical and health sciences; R5-920; Granulocyte Colony-Stimulating Factor; Genetics; Animals; mobilization; Mice, Knockout; 0303 health sciences; CoPP; Articles; Hematopoietic Stem Cells; Hematopoietic Stem Cell Mobilization; 3. Good health; Mice, Inbred C57BL; Female; granulocyte colony-stimulating factor; Heme Oxygenase-1; Granulocytes

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.