Abstract
Bone marrow stromal cells, including endothelial cells and mesenchymal stromal cells, support the maintenance, differentiation, and retention of hematopoietic stem and precursor cells under steady state conditions. At the onset of an emergency, such as severe blood loss or infection, the status of hematopoiesis in the bone marrow changes rapidly to ensure efficient production of cells of specific lineages; however, the function of stromal cells in emergency hematopoiesis has not been fully elucidated. Here, we unexpectedly found that B precursor, mature B, and T cells were released from the bone marrow into the blood circulation in the early phase of hemorrhagic anemia and phenylhydrazine-induced hemolytic anemia. Administration of erythropoietin, which normally increases in response to anemia, stimulated the egress of IgDlow immature B cells and recirculating mature B cells, which usually reside in the perivascular and intravascular space, from the bone marrow within 24 h. We also observed that endothelial cells in the bone marrow expressed erythropoietin receptor, and the expression levels were higher than those in other tissues. Erythropoietin stimulation of bone marrow endothelial cells induced the phosphorylation of STAT5 in vitro. Moreover, in vivo treatment with erythropoietin decreased surface VCAM1 expression and Cxcl12 transcription in bone marrow endothelial cells, both of which are essential for immature and mature B cell retention in the bone marrow. These results suggest that bone marrow endothelial cells can sense and rapidly respond to erythropoietin increase during anemia, thereby regulating B cell emigration from the bone marrow during emergency hematopoiesis.Key words: erythropoietin, anemia, endothelial cells, B cell, bone marrow microenvironment.
Highlights
Introduction hematopoietic cytokinesAcute anemia commonly occurs because of blood loss caused by severe trauma, various hemorrhagic disorders of the gastrointestinal tract, lung, and uterus, and, albeit less commonly, due to hemolytic anemia
B cells almost disappeared from the bone marrow, whereas the distribution of Gr-1+ neutrophils remained unchanged (Fig. 2F). These results indicate that erythropoietin rapidly promotes the release of newly formed immature B cells and recirculating mature B cells and T cells from the bone mar‐
These results indicate that bone marrow endothelial cells express functional erythropoietin receptor and can potentially respond to erythropoietin
Summary
Introduction hematopoietic cytokinesAcute anemia commonly occurs because of blood loss caused by severe trauma, various hemorrhagic disorders of the gastrointestinal tract, lung, and uterus, and, albeit less commonly, due to hemolytic anemia. Bone marrow microenvironments, including endothelial cells, mesenchymal stromal cells Vascular cells and Cxcl abundant reticular (CAR) cells), and osteoblasts, support hematopoiesis by producing cyto‐. Several reports have demonstrated that these bone marrow stromal cells rapidly respond to emer‐. Multilineage hematopoietic cells, including B cells, granulocytes, erythrocytes, and platelets, are produced in the bone marrow persistently throughout life. During emergency situations, such as bleeding or infection, the bone marrow rapidly produces massive numbers of specific lineages of hematopoietic cells, primarily in response to increased production of ment of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
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