Effect of Neopterin on Splenic Erythropoiesis in Mice

Pteridines ◽  
2010 ◽  
Vol 21 (1) ◽  
pp. 7-10 ◽  
Author(s):  
Isao Tsuboi ◽  
Tomonori Harada ◽  
Hideki Oshima ◽  
Shin Aizawa
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Pretreatment Level ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Extramedullary Erythropoiesis

Abstract Neopterin is produced by monocytes and is a biomarker for inflammation. We recently found that neopterin induces stromal cells to produce cytokines that suppress erythropoiesis in the bone marrow of mice. Despite this suppression, the peripheral hematocrit values are not decreased. The goal of the present study was to determine whether the maintenance of hematocrit values is caused by a neopterin-induced acceleration of extramedullary erythropoiesis. We examined the effects of intravenously injected neopterin on splenic erythropoiesis in C57BL/6J mice and found a marked increase (259% of the pretreatment level) in the number of splenic erythroid progenitor cells (BFU-E and CFU-E) after a slight temporal decrease in the number of erythroid progenitor cells. These results suggest that neopterin increases splenic erythropoiesis to compensate for the suppression of erythropoiesis in the bone marrow, resulting in the maintenance of hematocrit levels in peripheral blood.

scholarly journals Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor.

1995 ◽  
Vol 15 (6) ◽  
pp. 3147-3153 ◽  
Author(s):  
G A Blobel ◽  
C A Sieff ◽  
S H Orkin
Keyword(s):  
Bone Marrow ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Progenitor Cells ◽  
Erythroid Cell ◽  
High Dose ◽  
Dependent Manner ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5. We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures. To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes. We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen. ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1. GATA-1 and ER bind to each other in vitro in the absence of DNA. In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner. Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1. We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER. Interference with GATA-binding proteins may be one mechanism by which steroid hormones modulate cellular differentiation.

scholarly journals Roles for integrin very late activation antigen-4 in stroma-dependent erythropoiesis

Blood ◽  
1994 ◽  
Vol 83 (10) ◽  
pp. 2844-2850 ◽  
Author(s):  
N Yanai ◽  
C Sekine ◽  
H Yagita ◽  
M Obinata
Keyword(s):  
Progenitor Cells ◽  
Adhesion Molecules ◽  
Stromal Cells ◽  
Ligand Molecule ◽  
Erythroid Cells ◽  
Erythroid Progenitor ◽  
Hematopoietic Stem ◽  
Erythroid Progenitor Cells ◽  
Stem And Progenitor Cells ◽  
Activation Antigen

Abstract Adhesion molecules are required for development of hematopoietic stem and progenitor cells in the respective hematopoietic microenvironments. We previously showed that development of the erythroid progenitor cells is dependent on their direct adhesion to the stroma cells established from the erythropoietic organs. In this stroma-dependent erythropoiesis, we examined the role of adhesion molecules in erythropoiesis by blocking antibodies. The development of the erythroid cells on stroma cells was inhibited by anti-very late activation antigen-4 (VLA-4 integrin) antibody, but not by anti-VLA-5 antibody, although the erythroid cells express both VLA-4 and VLA-5. Whereas high levels of expression of vascular cell adhesion molecule-1 (VCAM-1) and fibronectin, ligands for VLA-4, were detected in the stroma cells, the adhesion and development of the erythroid progenitor cells were partly inhibited by the blocking antibody against VCAM-1. VLA-5 and fibronectin could mediate adhesion of the erythroid progenitor cells to the stromal cells, but the adhesion itself may not be sufficient for the stroma-supported erythropoiesis. The stromal cells may support erythroid development by the adhesion through a new ligand molecule(s) for VLA-4 in addition to VCAM-1, and such collaborative interaction may provide adequate signaling for the erythroid progenitor cells in the erythropoietic microenvironment.

scholarly journals Abnormal erythroid progenitor cells in human preleukemia

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 362-367 ◽  
Author(s):  
DH Chui ◽  
BJ Clarke
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Culture Technique ◽  
The Other ◽  
Erythroid Cell ◽  
Erythroid Progenitor ◽  
Clonal Culture ◽  
Erythroid Progenitor Cells ◽  
Marrow Cells

Abstract Ten patients with preleukemia were studied by the erythroid cell clonal culture technique. In nine of these patients, erythroid colonies derived from peripheral blood BFU-E were not observed, while the other patient had markedly decreased peripheral blood BFU-E-derived erythroid colonies in vitro. In three patients, marrow cells were also cultured and no BFU-E-derived erythroid colonies were detected. These studies indicate that immature erythroid progenitor cells, BFU-E, in patients with preleukemia are either markedly decreased in number or grossly defective in their proliferative or differentiative capacities.

scholarly journals Inhibition of Immature Erythroid Progenitor Cell Proliferation by Macrophage Inflammatory Protein-1α by Interacting Mainly With a C-C Chemokine Receptor, CCR1

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 605-611 ◽  
Author(s):  
Shao-bo Su ◽  
Naofumi Mukaida ◽  
Jian-bin Wang ◽  
Yi Zhang ◽  
Akiyoshi Takami ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Inflammatory Protein ◽  
Cd34 Cells ◽  
Macrophage Inflammatory Protein ◽  
Marrow Cells

Abstract Several lines of evidence indicate that macrophage inflammatory protein-1α (MIP-1α) modulates the proliferation of hematopoietic progenitor cells, depending on their maturational stages. To clarify the mechanisms for the modulation of hematopoiesis by this chemokine, we examined the expression of a receptor for MIP-1α, CCR1, on bone marrow cells of normal individuals using a specific antibody and explored the effects of MIP-1α on in vitro erythropoiesis driven by stem cell factor (SCF) and erythropoietin (Epo). CCR1 was expressed on glycophorin A-positive erythroblasts in addition to lymphocytes and granulocytes. CCR1+ cells, isolated from bone marrow mononuclear cells (BMMNCs) using a cell sorter, comprised virtually all erythroid progenitor cells in the BMMNCs. Moreover, MIP-1α inhibited, in a dose-dependent manner, colony formation by burst-forming unit-erythroid (BFU-E), but not by colony forming unit-erythroid (CFU-E), in a methylcellulose culture of purified human CD34+ bone marrow cells. Although reverse-transcription polymerase chain reaction (RT-PCR) showed the presence of CCR1, CCR4, and CCR5 transcripts in CD34+ cells in BM, anti-CCR1 antibodies significantly abrogated the inhibitory effects of MIP-1α on BFU-E formation both in a methylcellulose culture and in a single cell proliferation assay of purified CD34+ cells. Although the contribution of CCR4 or CCR5 cannot be completely excluded, these results suggest that MIP-1α–mediated suppression of the proliferation of immature, but not mature erythroid progenitor cells, is largely mediated by CCR1 expressed on these progenitor cells.

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