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.

4th Department of Internal Medicine and Institute of Medical Biochemistry and Laboratory Medicine 1st Faculty of Medicine Charles University Prague Prague Czech Republic

A Chelkowski Institute of Physics University of Silesia Chorzow Poland Silesian Center for Education and Interdisciplinary Research Chorzow Poland

Department of Medical Biotechnology Faculty of Biochemistry Biophysics and Biotechnology Jagiellonian University Krakow Poland

Department of Medical Biotechnology Faculty of Biochemistry Biophysics and Biotechnology Jagiellonian University Krakow Poland Department of Clinical Immunology and Transplantology Institute of Pediatrics Jagiellonian University Medical College Krakow Poland

Department of Medical Biotechnology Faculty of Biochemistry Biophysics and Biotechnology Jagiellonian University Krakow Poland Malopolska Centre of Biotechnology Jagiellonian University Krakow Poland