Journal
EMBO MOLECULAR MEDICINE
Volume 11, Issue 12, Pages -Publisher
WILEY
DOI: 10.15252/emmm.201809571
Keywords
CoPP; granulocyte colony-stimulating factor; hematopoietic stem and progenitor cells; HO-1; mobilization
Categories
Funding
- EU [01.02.00-069/09]
- National Science Center [NCN2015/18/M/NZ3/00387, NCN2013/11/N/NZ3/00956]
- Ministry of Science and Higher Education, Republic of Poland [1319/MOB/IV/2015/0, 1273/MOB/IV/2015/0]
- Ministry of Science and Higher Education
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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.
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