Hematopoietic Progenitor Cell Mobilization Results in Hypoxia with Increased Hypoxia-Inducible Transcription Factor-1α and Vascular Endothelial Growth Factor A in Bone Marrow
| Autor: | Ingrid G. Winkler, Jean Hendy, Susan K. Nilsson, Valerie Barbier, Brenda Williams, Jean-Pierre Levesque, Falak Helwani, Bianca Nowlan |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Bone Marrow Cells Mice Inbred Strains Vascular permeability Biology Capillary Permeability Mice Oxygen Consumption Bone Marrow Cell Movement Tumor Cells Cultured medicine Animals Progenitor cell Transcription factor Mice Inbred BALB C Hematopoietic stem cell Cell Biology Hematopoietic Stem Cells Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Cell biology Mice Inbred C57BL Haematopoiesis Vascular endothelial growth factor A medicine.anatomical_structure Gene Expression Regulation Nitroimidazoles Immunology Molecular Medicine Bone marrow Stem cell Granulocytes Developmental Biology |
| Zdroj: | Stem Cells. 25:1954-1965 |
| ISSN: | 1549-4918 1066-5099 |
| Popis: | Despite the fact that many hypoxia-inducible genes are important in hematopoiesis, the spatial distribution of oxygen in the bone marrow (BM) has not previously been explored in vivo. Using the hypoxia bioprobe pimonidazole, we showed by confocal laser scanning microscopy that the endosteum at the bone-BM interface is hypoxic, with constitutive expression of hypoxia-inducible transcription factor-1α (HIF-1α) protein in steady-state mice. Interestingly, at the peak of hematopoietic stem and progenitor cell (HSPC) mobilization induced by either granulocyte colony-stimulating factor or cyclophosphamide, hypoxic areas expand through the central BM. Furthermore, we found that HSPC mobilization leads to increased levels of HIF-1α protein and increased expression of vascular endothelial growth factor A (VEGF-A) mRNA throughout the BM, with an accumulation of VEGF-A protein in BM endothelial sinuses. VEGF-A is a cytokine known to induce stem cell mobilization, vasodilatation, and vascular permeability in vivo. We therefore propose that the expansion in myeloid progenitors that occurs during mobilization depletes the BM hematopoietic microenvironment of O2, leading to local hypoxia, stabilization of HIF-1α transcription factor in BM cells, increased transcription of VEGF-A, and accumulation of VEGF-A protein on BM sinuses that increases vascular permeability.Disclosure of potential conflicts of interest is found at the end of this article. |
| Databáze: | OpenAIRE |
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