title: SDF-1/CXCL12 modulates mitochondrial respiration of immature blood cells in a bi-phasic manner.
abstract: SDF-1/CXCL12 is a potent chemokine required for the homing and engraftment of hematopoietic stem and progenitor cells. Previous data from our group has shown that in an SDF-1/CXCL12 transgenic mouse model, lineage(-) Sca-1(+) c-Kit(+) (LSK) bone marrow cells have reduced mitochondrial membrane potential versus wild-type. These results suggested that SDF-1/CXCL12 may function to keep mitochondrial respiration low in immature blood cells in the bone marrow. Low mitochondrial metabolism helps to maintain low levels of reactive oxygen species (ROS), which can influence differentiation. To test whether SDF-1/CXCL12 regulates mitochondrial metabolism, we employed the human leukemia cell line HL-60, that expresses high levels of the SDF-1/CXCL12 receptor, CXCR4, as a model of hematopoietic progenitor cells in vitro. We treated HL-60 cells with SDF-1/CXCL12 for 2 and 24h. Oxygen consumption rates (OCR), mitochondrial-associated ATP production, mitochondrial mass, and mitochondrial membrane potential of HL-60 cells were significantly reduced at 2h and increased at 24h as compared to untreated control cells. These biphasic effects of SDF-1/CXCL12 were reproduced with lineage negative primary mouse bone marrow cells, suggesting a novel function of SDF-1/CXCL12 in modulating mitochondrial respiration by regulating mitochondrial oxidative phosphorylation, ATP production and mitochondrial content.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Messina-Graham
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, USA. Electronic address: hbroxmey@iupui.edu.
authors.forename: Hal
authors.initials: H
authors.lastname: Broxmeyer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D019069:Cell Respiration; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D000255:Adenosine Triphosphate
keywords: Blood cells; Mitochondria; Oxygen consumption; SDF-1/CXCL12