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Erythropoietin stimulates spleen BMP4-dependent stress erythropoiesis and partially corrects anemia in a mouse model of generalized inflammation
- Source :
- Blood. 116:6072-6081
- Publication Year :
- 2010
- Publisher :
- American Society of Hematology, 2010.
-
Abstract
- Mouse bone marrow erythropoiesis is homeostatic, whereas after acute anemia, bone morphogenetic protein 4 (BMP4)–dependent stress erythropoiesis develops in the spleen. The aim of this work was to compare spleen stress erythropoiesis and bone marrow erythropoiesis in a mouse model of zymosan-induced generalized inflammation, which induces long-lasting anemia and to evaluate the ability of erythropoietin (Epo) injections to correct anemia in this setting. The effects of zymosan and/or Epo injections on erythroid precursor maturation and apoptosis, serum interferon-γ levels, hematologic parameters, and spleen BMP4 expression were analyzed, as well as the effect of zymosan on red blood cell half-life. We found that bone marrow erythropoiesis is suppressed by inflammation and does not respond to Epo administration, despite repression of erythroblast apoptosis. On the contrary, a robust erythropoietic response takes place in the spleen after Epo injections in both control and zymosan-induced generalized inflammation mice. This specific response implies Epo-mediated induction of BMP4 expression by F4/80+ spleen macrophages, proliferation of stress burst-forming units-erythroid, and increased number of spleen erythroblasts. It allows only partial recovery of anemia, probably because of peripheral destruction of mature red cells. It is not clear whether similar BMP4-dependent stress erythropoiesis can occur in human bone marrow after Epo injections.
- Subjects :
- Male
medicine.medical_specialty
Anemia
Blotting, Western
Immunology
Apoptosis
Spleen
Bone Morphogenetic Protein 4
Biochemistry
Mice
chemistry.chemical_compound
Bone Marrow
Erythroblast
hemic and lymphatic diseases
Internal medicine
Receptors, Erythropoietin
medicine
Animals
Humans
Erythropoiesis
RNA, Messenger
Erythropoietin
Erythroid Precursor Cells
Inflammation
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Zymosan
Cell Biology
Hematology
medicine.disease
Recombinant Proteins
Mice, Inbred C57BL
Disease Models, Animal
Red blood cell
Haematopoiesis
medicine.anatomical_structure
Endocrinology
chemistry
business
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....6fcc44c052038ce574e4d7c7bf10ef7f