Cobalt Protoporphyrin IX Increases Endogenous G-CSF and Mobilizes HSC and Granulocytes to the Blood

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2019 Nov 12

PMID 31709729

Citations 8

Authors

Agata Szade

Krzysztof Szade

Witold N Nowak

Karolina Bukowska-Strakova

Lucie Muchova

Monika Gonka

Monika Zukowska

Maciej Ciesla

Neli Kachamakova-Trojanowska

Marzena Rams-Baron

Alicja Ratuszna

Jozef Dulak

Alicja Jozkowicz

Affiliations

Soon will be listed here.

Abstract

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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