Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Erythroid Precursor Cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed1989

Activated macrophages distinguish undifferentiated-tumorigenic from differentiated-nontumorigenic murine erythroleukemia cells.

The interaction between macrophages and differentiating cells was examined using murine erythroleukemia cells (MELC). Inflammatory macrophages activated with recombinant murine interferon-gamma (rMuIFN-gamma) and lipopolysaccharide (LPS) first specifically recognized and bound tumorigenic-undifferentiated MELC and then produced their lysis. MELC that were induced to differentiate by a 5-day treatment with 5 mM N,N'-hexamethylene-bis-acetamide (HMBA) accumulated hemoglobin (benzidine positive) and were not recognized by the macrophages. Qualitative examination by light and electron microscopy confirmed the specific nature of the macrophage-MELC interaction. Quantitative assessment showed that the binding was dependent on the temperature and divalent cations and independent of serum components. A 24-h treatment of MELC with HMBA resulted in decreased binding, prior to hemoglobin accumulation and commitment to differentiation. The lack of binding of nontumorigenic-differentiated cells by macrophages was not due to residual HMBA. It thus appears that macrophages can distinguish MELC at different stages of differentiation.

Animals↗
PubMed1993

Common antigen of oval and biliary epithelial cells (A6) is a differentiation marker of epithelial and erythroid cell lineages in early development of the mouse.

The A6 antigen--a surface-exposed component shared by mouse oval and biliary epithelial cells--was examined during prenatal development of mouse in order to elucidate its relation to liver progenitor cells. Immunohistochemical demonstration of the antigen was performed at the light and electron microscopy level beginning from the 9.5 day of gestation (26-28 somite pairs). Up to the 11.5 day of gestation A6 antigen is found only in the visceral endoderm of yolk sac and gut epithelium, while liver diverticulum and liver are A6-negative. In the liver epithelial lineages A6 antigen behaves as a strong and reliable marker of biliary epithelial cells where it is found beginning from their emergence on the 15th day of gestation. It was not revealed in immature hepatocytes beginning from the 16th day of gestation. However weak expression of the antigen was observed in hepatoblasts on 12-15 days of gestation possibly reflecting their ability to differentiate along either hepatocyte or biliary epithelial cell lineages. Surprisingly, A6 antigen turned out to be a peculiar marker of the crythroid lineage: in mouse fetuses it distinguished A6 positive liver and spleen erythroblasts from A6 negative early hemopoietic cells of yolk sac origin. Moreover in the liver, A6 antigen probably distinguishes two waves of erythropoiesis: it is found on the erythroblasts from the 11.5 day of gestation onward while first extravascular erythroblasts appear in the liver on the 10th day of gestation. Both fetal and adult erythrocytes are A6-negative. In the process of organogenesis A6 antigen was revealed in various mouse fetal organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

The role of tyrosine phosphorylation in proliferation and maturation of erythroid progenitor cells--signals emanating from the erythropoietin receptor.

Red blood cells arise continuously from pluripotent stem cells which mature and become functionally specialized upon commitment to the erythroid lineage. In mammals, the key regulator of this process is the hormone erythropoietin (EPO). Hormone binding to the cognate receptor, the erythropoietin receptor (EPO-R), causes receptor homodimerization and transiently triggers tyrosine phosphorylation within target cells. Although the EPO-R lacks intrinsic enzymatic activity it couples, presumably sequentially, to the protein tyrosine kinase receptor c-KIT and the cytosolic protein tyrosine kinase JAK2. Signaling through the EPO-R is promoted by tyrosine phosphorylation of the cytosolic domain and the recruitment of secondary signaling molecules such as the lipid kinase inositolphospholipid 3-kinase (phosphatidylinositol 3-kinase) and protein tyrosine phosphatase SHP-2 to the activated receptor. Complex formation of the activated EPO-R with the protein tyrosine phosphatase SHP-1 terminates signaling. In primary fetal liver cells redundant signals emanating from phosphotyrosine residues in the EPO-R support formation of erythroid colonies in vitro. However, since the last tyrosine residue in the cytosolic domain of the EPO-R, Y479, uniquely supports in the absence of other tyrosine residues an almost normal level of colony-forming unit-erythroid (CFU-E) colony formation, Y479 represents one of the key residues required in vivo for erythroid proliferation and differentiation. The signal emanating from Y479 involves sequential EPO-induced recruitment of phosphoinositol lipid 3-kinase to the EPO-R and activation of mitogen-activated-protein(MAP)kinase activity. The MAP-kinase signaling cascade could serve as an intracellular switch integrating signals mediated by several phosphotyrosine residues in the cytosolic domain of the EPO-R and provide a possible explanation for partial redundancy in signaling.

Animals↗
PubMed1991

A liquid culture method for the in vitro growth of hemopoietic progenitor cells from normal human adult peripheral blood allowing for analysis by multiparameter flow-cytometry.

A liquid culture method has been developed allowing for the in vitro growth of peripheral blood-derived hemopoietic progenitor cells of myeloid, erythroid, monocytic and megakaryocytic lineages. Adherent cell- and CD21-positive cell-depleted PBMC from normal subjects have been cultured in the presence of rhEPO, rhGM-CSF or rhIl-3. Culturing cells in liquid cultures and in plasma clots, a similar dose-response was observed for granulocytic cells/liquid culture and granulocytic colonies/plasma clot with rhGM-CSF, and also for erythroid cells/liquid culture and erythroid colonies/plasma clot with rhEPO. Comparing serum- liquid cultures to serum+ liquid cultures, the ratio of CD13+ cells to CD15+ cells was higher in serum- cultures, indicating a maturation arrest of myecloid cells with serum deprivation. Using dual-colour flow-cytometry, cell-cycle analysis of CD13+ cells, comparing the effects of rhGM-CSF to those of rhIl-3, have been performed. The liquid culture method promises to be a useful tool for the study of in vitro differentiation and proliferation of hemopoietic progenitor cells.

Adult↗
PubMed1992

Identification of a normal human bone marrow cell population co-expressing megakaryocytic and erythroid markers in culture.

A population of haematopoietic cells co-expressing glycoprotein IIIa (GPIIIa), which has been shown to be present in the megakaryocyte-platelet lineage, and glycophorin A, which has been shown to be specific for the erythroid lineage, has been identified in normal bone marrow cultures using double immunofluorescence staining. The cells showing this phenotype have the size of lymphocytes and appear at an early time (day 1 to d 6) of culture. We have also detected a type of mixed megakaryocyte (MK) cluster containing this phenotype on d 3 or 4 in most normal marrow samples. Such a cell phenotype was not detected after 6 d of culture. It is thus the first time that this phenotype, although already described for several human neoplastic cell lines, has been observed in several normal human bone marrow cultures. Cells expressing this phenotype may represent haematopoietic cells, common to megakaryocytic and erythroid lineages, at a very early stage of differentiation.

Biomarkers↗
PubMed1993

The in vitro effects of interferon-gamma, interferon-alpha, and tumour-necrosis factor-alpha on erythroid burst-forming unit growth in patients with non-leukaemic myeloproliferative disorders.

We have studied the effects of interferons gamma (IFN-gamma) and alpha (IFN-alpha), and tumour-necrosis factor-alpha (TNF) on circulating 14-day erythroid progenitor cell (BFU-E) growth in vitro from patients with non-leukaemic myeloproliferative disorders (MPD) compared with normal controls. IFN-gamma (1000 U/ml) inhibited BFU-E growth in all controls studied (mean growth +/- SE = 61% +/- 6%, n = 10). In 7 of 11 MPD studied there was no inhibition, and in some cases clear enhancement of BFU-E growth by IFN-gamma. When cultured in the presence of recombinant erythropoietin (rEpo) 1 U/ml, both IFN-alpha and TNF (at 100 and 1000 U/ml) produced a similar degree of inhibition of BFU-E growth in MPD and controls. The inhibition by 100 U/ml IFN-alpha was abrogated, partially in controls but completely in MPD, by increasing the dose of rEpo to 5 U/ml. Similarly, the increase in rEpo dose enhanced BFU-E growth in cultures with 100 U/ml TNF, but had little effect on cultures containing 1000 U/ml of either IFN-alpha or TNF. The aberrant in vitro response to IFN-gamma demonstrated in some of these patients may be of relevance to the pathophysiology of MPD. These results fail to demonstrate a differential in vitro effect for IFN-alpha on MPD BFU-E growth compared with controls and suggest that the in vitro suppression of haemopoiesis by IFN-alpha when used in MPD treatment is non-specific.

Cells, Cultured↗
PubMed1994

Idiopathic erythrocytosis--additional new study techniques suggest a heterogenous group.

25 patients with idiopathic erythrocytosis (absolute increase in red cell mass without conventional criteria of primary polycythaemia or known underlying cause) have been further studied for evidence of primary or secondary polycythaemia. Additional non-conventional criteria used were: platelet distribution width, platelet nucleotide ratio, serum erythropoietin, clinical evidence of ischaemic vascular disease and erythroid culture variables in serum-free system. All had been used in an earlier study in score form to assist in the diagnosis of primary polycythaemia. These patients were also newly assessed for the presence of hypoxia (supine oximeter values, history suggestive of sleep apnoea), for renal lesions and for splenic enlargement (impalpable) by ultrasound or computerized tomography. 7 patients had erythroid culture scores suggesting primary polycythaemia but the addition of non-culture criteria did not result in any scores more strongly predictive of primary polycythaemia. Supine oximeter values < 92% suggested hypoxaemia as the mechanism of polycythaemia in 3 patients in whom it had not previously been suspected. Some splenic enlargement (impalpable) was demonstrated in 6 patients, only 1 of whom had erythroid culture scores suggesting primary polycythaemia. 12 patients had confirmed, raised erythropoietin levels. We conclude that idiopathic erythrocytosis refers to a heterogenous group of patients. Features of primary or secondary polycythaemia may be demonstrated in some of them by additional new study techniques. The raised erythropoietin values found in half the patients were unexpected.

Adolescent↗
PubMed1998

In vitro effect of stem cell factor on human clonogenic marrow progenitors after myeloablative treatments.

Abnormal hematopoiesis, including a deficiency of marrow progenitors and particularly of erythroid progenitors, has been described after autologous stem cell transplantation (ASCT), persisting for several years. In order to explain this deficiency, a resistance of marrow progenitors to stem cell factor (SCF) after ASCT was investigated. Marrow samples were harvested from pregraft patients at graft collection prior to ASCT, transplanted patients 6-24 months after high-dose therapy and control patients. CD34+ cells were cultured in a serum-free clonogenic assay with increasing doses of SCF. The clonogenic efficiency without SCF was lower for BFU-E in treated groups than in controls, whereas it was not different for CFU-GM. With increasing doses of SCF a dose-dependent effect was found on the numbers of both CFU-GM and BFU-E in all groups, although the maximal number of BFU-E remained lower in treated groups. However, the SCF dose that induced 50% of maximal BFU-E growth (D50) was similar in all groups. Furthermore, a dose-dependent effect on the size of BFU-E was found in all groups, with no difference in the proportion of large colonies. Thus, clonogenic erythroid progenitors from patients who have received myelotoxic treatments remain sensitive to SCF, with no evidence for a chemotherapy-related resistance.

Adult↗
PubMed1994

Clinical trials and experience: Boston.

Our cumulative experience continues to validate the fetal nucleated erythrocyte as the target fetal cell type of choice, primarily because it reflects the cytogenetic status of the current pregnancy. Additional cell types, such as the granulocyte, await further study. Quantitative PCR is a sensitive and useful new method that can facilitate rapid comparisons between cell separation methods or different monoclonal antibodies. It can also be used on patient material to determine final purity of the enriched maternal samples. If the purity is too low, FISH studies will be complicated by the presence of thousands of maternal cells. Our planned studies include an analysis of why aneuploid pregnancies appear to have a higher number of fetal cells in the maternal circulation. We are also studying the timing of the fetomaternal transfer of cells with qPCR analysis of sorted maternal samples drawn weekly from well-dated women. We are continuously improving our methods (both in separations and antibodies) to reach a fetal cell purity of at least 20% for cytogenetic diagnosis by FISH studies. With the knowledge obtained thus far by us and by others, such a goal appears to be achievable within the near future.

Antibodies, Monoclonal↗
PubMed2002

Preexisting immunity to adenovirus in rhesus monkeys fails to prevent vector-induced toxicity.

In an earlier study we evaluated innate immune responses to a first-generation adenoviral vector infused into the portal vein of rhesus monkeys who had never been exposed to adenovirus previously. In these animals, the systemic administration of E1/E3-deleted adenoviral vectors resulted in immediate activation of innate immunity and serious toxicity caused by targeting of vector to antigen-presenting cells and systemic inflammation. We analyze here how these responses are affected by vector-specific preexisting immunity that was induced by intramuscular immunization 6 months prior to evaluation. Our results show that preexposure to the vector substantially diminishes the transgene expression in most tissues but has little effect on gene transfer. Significantly, preimmunization does not eliminate systemic vector-induced toxicity. These conclusions are based on the presence of clinical features of coagulopathy and elevated levels of proinflammatory cytokine interleukin-6 in the serum of animals treated with vector after intramuscular immunization. Furthermore, preexisting immunity appears to induce a vector-specific inhibitory effect on erythroid progenitor development in the bone marrow that is not found when naive animals are challenged with vector.

Adenoviruses, Human↗
PubMed1991

Regulated expression of human alpha- and beta-globin genes in transient heterokaryons.

We have examined the expression of human alpha- and beta-like globin genes in transient heterokaryons formed by fusion of human nonerythroid cells with terminally differentiating mouse erythroleukemia (MEL) cells or with a MEL cell variant (GM979) in which the endogenous mouse embryonic beta-globin genes are activated. In both the parental MEL cells and the heterokaryons, the alpha-globin genes were activated at least 12 h earlier than the embryonic, fetal, and adult beta-globin genes. These results suggest that kinetic differences in the activation of alpha- and beta-like globin genes are not simply the result of different rates of accumulation of erythroid-specific regulatory factors but may reflect differences in the mechanisms governing the transcriptional activation of these genes during erythroid cell differentiation. In mouse GM979 x human nonerythroid heterokaryons, the human embryonic beta-globin gene was activated, consistent with our previous demonstration that erythroid cells contain stage-specific trans-acting regulators of globin gene expression. Moreover, a dramatic increase in the ratio of human fetal to adult beta-globin transcription was observed compared with that seen in MEL-human nonerythroid hybrids. This ratio change may reflect competition between the fetal and adult beta-globin genes for productive interactions with erythroid cell-specific regulatory elements. Finally, we demonstrate that the behavior of naturally occurring mutations that lead to aberrant hemoglobin switching in humans also leads to aberrant expression in transient heterokaryons. Therefore, erythroid cells must contain trans-acting factors that interact with mutated regulatory elements to induce high-level expression of the human fetal globin genes.

Cell Fusion↗