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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood mononuclear cells from patients with polycythemia vera or myelofibrosis with myeloid metaplasia were studied for their erythroid colony growth characteristics in plasma clot cultures. In both diseases, erythroid colonies formed early in culture in the absence of added erythropoietin (endogenous colonies). In no instance did early, endogenous colony formation occur with peripheral blood cells from normals or patients with secondary polycythemia. A normal response to erythropoietin was observed with both control and patients' peripheral blood cells. Spleen mononuclear cells obtained from one patient with myelofibrosis also produced endogenous colonies and showed a response to erythropoietin. This study suggests that culture of peripheral blood mononuclear cells might serve as a useful tool in discriminating polycythemia vera from secondary polycythemia.
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PMID:Endogenous erythroid colony formation by peripheral blood mononuclear cells from patients with myelofibrosis and polycythemia vera. 11 8

A single dose of erythropoietin stimulates DNA synthesis in the spleen of the polycythemic mouse with the maximum effect occurring 48 h after the hormone is administered. The increase in DNA synthesis is accompanied by morphologic evidence of increased erythropoiesis and by increases in the activities per cell of both thymidine kinase and cytoplasmic high molecular weight DNA polymerase-alpha. The activity of low molecular weight DNA polymerase-beta does not change significantly. Spleen cells from mice which had received either erythropoietin or saline 48 h previously were separated into 7 density classes on discontinuous bovine serum albumin gradients. Following the administration of erythropoietin, thymidine incorporation and thymidine kinase activity showed the greatest relative increases per nucleated cell in layers 3, 4 and 5 of the gradient. DNA polymerase-alpha showed the greatest increase in cells of the denser layers 5, 6 and 7. Each layer contained normoblasts and lymphocytes. The less well differentiated erythroid elements constituted a larger proportion of cells in layers of lower density. Increases in the rates of thymidine incorporation were better correlated with increases in thymidine kinase activity than with increases in DNA polymerase activities. Measurement of iron incorporation into heme confirm the morphological impression that the cell type responsible for increased thymidine incorporation and increased DNA polymerase-alpha activity is the young normblast.
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PMID:DNA polymerase, thymidine kinase and DNA synthesis in erythropoietic mouse spleen cells separated on bovine serum albumin gradients. 125 82

ME26 virus, which was generated by inserting the coding region of the acute avian leukemia-inducing virus E26 into a murine retrovirus vector, encodes a 135-kDa gag-myb-ets fusion protein. Amphotropic murine leukemia virus pseudotypes of ME26 virus induce a high incidence of erythroleukemia 2 to 4 months after injection into newborn NFS/N mice. Spleen cells from the majority of these mice proliferate to high levels in the presence of the erythroid hormone erythropoietin (Epo) and can easily be established as permanent Epo-dependent cell lines. The cell lines contain multiple copies of ME26 viral DNA and express viral message and protein. An Epo receptor mRNA of normal size can be detected in these cells, and binding studies reveal a single class of lower-affinity Epo receptor with an affinity for Epo that is in the range of that previously reported for erythroid cells. The ME26 virus-induced Epo-dependent cell lines, however, appear more immature than previously described erythroid cell lines and more closely resemble early hematopoietic precursor cells, suggesting that the virus may be activating the Epo receptor in hematopoietic cells that do not normally express it. Consistent with this idea, we are able to infect an interleukin-3-dependent myeloid cell line, FDC-P2, with ME26 virus and convert it to Epo dependence. The ME26 virus-infected FDC-P2 cells, even before growth on Epo, showed a large increase in the amount of Epo receptor mRNA. However, no ME26 viral integrations can be detected adjacent to the Epo receptor gene, indicating that the virus is not activating the Epo receptor gene by promoter/enhancer insertion. Our results are more consistent with the hypothesis that the gag-myb-ets-encoded viral fusion protein, which is known to bind DNA, is directly or indirectly activating the expression of the Epo receptor gene in these cells.
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PMID:Induction of erythropoietin responsiveness in murine hematopoietic cells by the gag-myb-ets-containing ME26 virus. 130 43

C57BL/6J murine bone marrow cells, infected with a retroviral vector (MP Zen) carrying a monkey erythropoietin cDNA, were transplanted into lethally irradiated syngeneic recipients to study the effect of erythropoietin production by hemopoietic cells. High levels of erythropoietin were recorded in the plasma (median value: 1.2 u/ml) and in media conditioned by peritoneal, spleen, and bone marrow cells from recipient mice. In transplanted mice, the hematocrit was elevated (90 +/- 5%) and the mice died at a mean of 71 days after transplantation. In the blood, platelet counts were usually low and nucleated blood cells slightly elevated. Spleen weight increased 5-fold and bone marrow cellularity decreased slightly. There was a 9.9-fold increase in erythroblast numbers, a 2-fold reduction of lymphocytes, and no variation of the myeloid cells when the total cellularity of bone marrow, spleen, peripheral blood, and peritoneal cells were considered. Calculation of the total numbers of progenitor cells in these organs revealed a 18-fold increase in erythroid colony-forming units (CFU-E) but no significant variation of the erythroid burst-forming units (BFU-E), and myeloid progenitor cell numbers. A variable proportion of CFU-E, (12% or 24% in bone marrow or spleen, respectively) was able to proliferate in unstimulated cultures. Erythropoietic amplification occurred in the spleen and there was a redistribution of the BFU-E and myeloid cells from the bone marrow to the spleen. No significant extramedullary erythropoiesis was seen. This study emphasizes the erythroid specificity of erythropoietin and shows that elevated dysregulated erythropoietin production by hemopoietic cells leads to a fatal polycythemia without erythroid neoplastic transformation.
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PMID:Fatal polycythemia induced in mice by dysregulated erythropoietin production by hematopoietic cells. 155 41

In order to investigate the role of the human spleen on hematopoiesis, hematopoietic stem cells and stimulates were evaluated in fetal and adult spleens. BFU-E and CFU-C were existed in 20 weeks and 23 weeks fetal spleens (BFU-E 145 +/- 45/10(5) mononuclear cells, CFU-C 55 +/- 6/10(5) mononuclear cells). In adult spleen, a few stem cells were recognized, which may be contaminated from peripheral blood in sinus of the spleen. We tested conditioned media from adult spleen cells for the stimulative activity on the in vitro growth of BFU-E and CFU-C from bone marrow mononuclear cells. Spleen conditioned medium stimulated proliferation of these precursor cells. It seemed that PHA-stimulated spleen conditioned medium augmented BFU-E, whereas CFU-C growth was suppressed. Adult and fetal spleens were studied immunohistochemically using anti-G-CSF, GM- CSF and erythropoietin antibodies. The cells with G-CSF and GM-CSF were shown in fetal spleens. In adult spleens, however, only GM-CSF was detected.
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PMID:[Spleen and hematopoiesis]. 260 Oct 40

This work characterizes the erythropoietic interplay of the spleen, blood, and bone marrow in a lethal murine malaria, strain 17XL P. yoelii. This malaria runs a fulminant 7 day course in BALB/c/ByJ mice, marked by high levels of parasitized reticulocytes with death likely due to anemia. We have quantitated the levels of burst forming units-erythroid (BFU-E), the early, niche-seeking, largely erythropoietin-unresponsive erythropoietic precursors, and of colony forming units-erythroid (CFU-E), the more differentiated sessile erythropoietin-responsive precursors, in bone marrow, blood, and spleen, through the course of this malaria. A decline in marrow BFU-E began on day 2, but recovered, relatively, after day 3. Marrow cellularity declined, being but 75% normal on day 6. Spleen weight increased about 5-fold within 6 days with enlargement of erythroid, lymphoid, macrophage, and stromal compartments. Splenic BFU-E increased in the first 24 hr and 5-fold by day 6. Splenic CFU-E increased in the first 24 hr and into day 4. They then declined and showed a secondary, large-scale, sustained rise interrupted by death. Because the spleen was enlarging, a greater than 60-fold increase in the absolute number of splenic CFU-E occurred at the time of death. Marrow CFU-E followed the same pattern as splenic CFU-E, but the terminal increase represented but a 4-fold absolute increase because of declining marrow cellularity. High levels of erythropoietin occurred only late in the course of disease, likely in response to profound anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of splenic control of murine malaria: tissue culture studies of the erythropoietic interplay of spleen, bone marrow, and blood in lethal (strain 17XL) Plasmodium yoelii malaria in BALB/c mice. 277 62

We have studied the hematopoietic system of the immunodeficient mouse mutant, viable motheaten (mev/mev). These mice usually die by 9 weeks of age from severe pneumonitis. The lungs at that time are infiltrated with granulocytes, macrophages, and lymphocytes. Granulocyte and macrophage precursor cells (CFU-GM) are dramatically increased in the spleens of mev/mev mice, whereas the bone marrow population of these precursors is decreased when compared with littermate control animals. The CFU-GM population retained its normal dependence on granulocyte-macrophage colony-stimulating factor (GM-CSF) for proliferation and differentiation. In contrast, the frequency of an erythroid precursor (CFU-E) was dramatically increased in spleen and showed increased sensitivity to erythropoietin (Epo). Moreover, a splenic CFU-E subpopulation formed normally appearing erythroid colonies in the absence of exogenous Epo. The bone marrow CFU-E population was significantly diminished in size when compared with either wildtype C57BL/6J mice or mice heterozygous for the mev allele. Unlike the CFU-E population, erythroid burst-forming unit (BFU-E) frequency in mev/mev mice was diminished both in bone marrow and in spleen, although the total number of splenic BFU-E was increased because of splenomegaly in these animals. BFU-E retained their dependence on the presence of both Epo and a source of interleukin 3 (IL-3) for proliferation and differentiation into erythroid bursts. Spleen cells from mev/mev mice, when stimulated in vitro with pokeweed mitogen, failed to produce significant quantities of IL-3. Comparison with medium or +/mev heterozygotes revealed that mev/mev spleen cell-conditioned medium showed a 40-fold reduction in burst-promoting activity. Thus, in viable motheaten mice, there is a major shift in hematopoiesis from bone marrow to spleen, which is accompanied by a diminished capacity of spleen cells to produce burst-promoting activity. These data and those from other studies suggest that the hematopoietic microenvironment of marrow may be impaired in this mutant.
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PMID:Hematologic abnormalities of the immunodeficient mouse mutant, viable motheaten (mev). 278 74

It has been shown that radiolabeled erythropoietin (epo) specifically binds to homogeneous epo-responsive spleen cells from mice infected with the anemic variant of the Friend virus. We now report that membranes isolated from these cells retain the ability to specifically bind epo. Spleen cells were swollen in ice-cold 10 mM Tris-Cl pH 7.4 containing 0.2 mM phenylmethyl sulfonylfluoride for 5 minutes, after which the cells were homogenized and centrifuged to remove nuclear fraction. Membranes were collected by centrifuging the supernatant at 75,000 g for 90 min. Utilizing 3H-epo labeled at the terminal sialic acids of the carbohydrate moieties or 125I-epo labeled at the tyrosine residues, it was shown that the isolated membranes contained specific epo binding sites. About 90% of the binding could be inhibited by the presence of unlabeled epo whereas no inhibition was seen with other glycoproteins and growth factors. Equilibrium could be reached in approximately 2.5 hr at 25 degrees C or 1.5 hr at 37 degrees C. Binding could be saturated at an epo concentration of about 3 nM, Scatchard analysis indicated a single class of receptors with a Kd of approximately 1.5 nM.
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PMID:Identification of erythropoietin receptors in isolated membranes from Friend virus infected mice spleen cells. 284 5

The simple, specific and sensitive erythropoietin bioassay in serum and plasma from phenylhydrazine treated mice is described, based on H3-thymidine incorporation into divided hemopoietic cells. Spleen cells taken from mice on the third day following the second of 2 daily injections of phenylhydrazine were cultured in 24 hours in the presence of test material. Following incubation for 2 hours with H3-thymidine solution radioactivity was measured.
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PMID:[Determination of serum and plasma erythropoietin in mice with phenylhydrazine-induced anemia]. 291 66

In order to clarify the mechanism(s) of increased splenic hematopoiesis noted in lipopolysaccharide (LPS)-injected mice, the effects of spleen cell-conditioned medium (SPCM) on megakaryocyte colony (CFU-meg) formation and early erythroid (BFU-e) differentiation were investigated. After spleen cells from LPS-injected mice were incubated for 3 days, the SPCM was assayed for megakaryocyte colony-stimulating factor (Meg-CSF) in CFU-meg assay and for burst-promoting activity (BPA) and erythropoietin (Epo) in erythroid colony assays (i.e., CFU-e, BFU-e). Colony formation of CFU-meg and BFU-e peaked with the addition of 30 and 10-15% SPCM, respectively. Spleen cells from LPS-injected mice produced Meg-CSF and BPA when compared with controls. However, conditioned medium from spleen cells depleted of phagocytic cells had low Meg-CSF and BPA. SPCM did not contain detectable quantities of Epo. It appears likely that local splenic production of Meg-CSF and BPA may affect proliferation of CFU-meg and erythroid progenitor cells in the spleen.
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PMID:Megakaryocyte colony-stimulating factor and burst-promoting activity in LPS-treated mouse spleen cell-conditioned medium. 326 23


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