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Results for “Erythroid Precursor Cells”

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PubMed1984

Effects of thymocytes on marrow cells from normal and busulfan-treated mice.

To study the effects of thymocytes on hemopoiesis, we 1) cocultured marrow cells with and without thymocytes in an erythroid burst (BFU-E) culture system, 2) injected marrow cells with and without thymocytes into supralethally irradiated mice to assay CFU-S, and 3) assessed the survival of supralethally irradiated mice transplanted with marrow cells with or without thymocytes. The marrow cells used were either from mice given six injections of busulfan and then permitted to rest for 2, 5, or 10 weeks or from mice treated similarly with the busulfan vehicle alone. Thymocytes did not alter spleen surface colony counts or survivorship in any of the test groups. Thymocytes did effect an increase in BFU-E cultured from marrow obtained from the vehicle-treated mice but not from marrow of busulfan-treated mice. Thus, in addition to decreasing the population of hemopoietic precursors in the marrow, busulfan alters the nature of the remaining early erythroid precursor cell population rendering it unresponsive to thymocytes in vitro.

Animals↗

PubMed1976

Chromosomes and causation of human cancer and leukemia. XIII. An evaluation of karyotypic findings in erythroleukemia.

This study was an attempt at defining the cytogenetic features of erythroleukemia (EL), particularly as related to the group of AML patients with MAKA (major karyotypic abnormalities), which generally were caused by three or more cellular events of translocation or nondisjunction. Eight of the 17 patients with MAKA had a diagnosis of EL or possible EL. In most cases, MAKA was featured by hypodiploidy, karyotypic instability, and polyploidy in the leukemic cells. The most common abnormalities were loss of B or G group chromosomes and gain of a no. 16 or one or more marker chromosomes. Each of the markers of 2q+, Dq+, mar(A2, st), mar(C12, M), r(?F) and minute metacentric and acentric markers was observed in two or more patients. The extent of polyploidy seemed to be correlated with the proportion of erythroid precursor cells in the marrow and with the karyotypic instability. Since the patients exhibited the same chromosomal features, whether or not they had a diagnosis of EL or possible EL, and since patients without such a diagnosis also had cytologic suggestions of EL, a close relation of MAKA to EL is assumed. It is believed that patients with MAKA constitute one of the three chromosomally classifiable groups of EL.

Bone Marrow↗

PubMed1987

Pure erythropoietic colony and burst formations in serum-free culture and their enhancement by insulin-like growth factor I.

Recombinant human insulin-like growth factor I (IGF-I) increased human and murine erythropoietic colony formation in serum-free culture. In order to investigate the effects of purified factors such as IGF-I on hemopoietic progenitor cells, we have established a serum-free culture system which supports the clonal growth of CFU-E- and BFU-E-derived colonies. Exogenously supplied ingredients were bovine serum albumin (BSA), transferrin, lipid suspensions, 2-mercaptoethanol, and recombinant human erythropoietin (epo). Among these, BSA and cholesterol were found to be essential ingredients. The optimum concentration of BSA sufficient to grow BFU-E was 3%. Erythroid colony and burst formation of human and murine marrow cells was enhanced twofold (p less than 0.05) by a physiological concentration of recombinant human IGF-I. Potentiation was observed in a dose-dependent manner between 10(-9) and 10(-7) M. A few murine CFU-E colonies were formed in the absence of epo. These results suggest that IGF-I has a supportive effect on the proliferation and differentiation of erythroid precursor cells stimulated by epo and that its action is synergistic with that of epo.

Animals↗

PubMed1987

Murine retrovirus-induced malignant histiocytosis, an experimental model for the disease in humans.

The hematopoietic disregulation in adult mice induced by the malignant histiocytosis sarcoma virus (MHSV) and the Harvey murine sarcoma virus (Ha-MuSV), which both possess c-Ha-ras-related oncogenic sequences, was investigated. Spleen focus formation induced by MHSV and Ha-MuSV was not restricted by the Fv-2 resistance locus in congenic DDD and C57BL/6 mice, unlike leukemogenesis induced by Friend virus, Rauscher virus, and the myeloproliferative sarcoma virus (MPSV). C57BL/6 mice were much more resistant to MHSV and Ha-MuSV-induced spleen focus formation than DDD mice regardless of their Fv-2 state. Infection of DDD mice with MHSV caused a systemic histiocytic neoplasia, best described as murine malignant histiocytosis. Transformed histiocytic cells proliferated excessively in the bone marrow, spleen, and lymph nodes and, in the final stages of the disease, in all major parenchymal organs. The Ha-MuSV caused a strikingly different benign histiocytic tumor in DDD mice and, unlike MHSV, did not induce a rapid, progressive splenomegaly in C57BL/6 mice. Infection of DDD mice with MHSV induced a rapid and synchronized depletion of early and late erythroid precursor cell pools. In MHSV-infected C57BL/6 mice comparable changes were observed with dissimilar kinetics. Macrophage colony-forming cells of MHSV-infected mice were increased in number and proliferated independently of stimulating growth factors. The disease induced by MHSV in mice can thus serve as a model for malignant histiocytosis in humans.

Animals↗

PubMed1990

Pyruvate kinase deficiency.

Pyruvate kinase (PK) deficiency was initially described by Valentine et al. in 1961. Since then, more than 300 cases have been described, including 65 in Japan. PK deficiency is the most common hereditary nonspherocytic hemolytic anemia among several red cell enzyme defects of the Embden-Meyerhof glycolytic pathway. The clinical manifestations are highly variable. Splenectomy usually increases the hemoglobin level by about 2 g/100 mL. Standardization of methods for characterization of PK variants was achieved in 1979. There are four PK isozymes, M1, M2, L and R, in mammalian tissues. We have clarified the switch from M2-type to L-type PK during maturation of erythroid precursor cells. Recently we cloned and sequenced a full length human L-type PK cDNA. It will be useful to clarify the molecular basis of PK deficiency.

Anemia, Hemolytic, Congenital↗

PubMed1984

Hemin-induced conversion of pyruvate kinase isozymes in K562 cells.

The effects of hemin on the conversion of pyruvate kinase (PK) isozymes from the M2-type to the L-type in K562 cells were investigated. Immunofluorescence, ion exchange chromatography, and electrophoretic studies showed that the untreated K562 cells contained only the M2-type PK, while eight to 20 days after induction with hemin, concomitant with hemoglobin F synthesis, L-type PK levels increased while M2-type PK levels decreased. Electrophoretic study revealed three hybrid isozymes of the L-type and M2-type PK. We conclude that the conversion of PK isozymes from the M2-type to the L-type in erythroid precursor cells occurs in the early stage of maturation.

Cell Line↗

PubMed2002

Cellular specificity related to monoglyceride-induced cell death.

We have recently observed that monoglycerides (MGs), a family of lipids consisting of a single fatty acid moiety attached to a glycerol backbone, induce rapid dose-dependent apoptosis in murine thymocytes. In this work, we evaluated the sensitivity of various normal and malignant immune and non-immune cells to MGs. We demonstrate that the propensity to MG-induced death displayed by both T and B lymphocytes is clearly modulated according to their differentiation and activation status. For instance, the earliest T and B cell precursors are refractory to MG-mediated cell death. In the T-cell lineage, immature thymocytes are the most susceptible to MG treatment, while B cells from peripheral lymphoid organs appear more sensitive than B-cell subsets from the bone marrow. On the other hand, both activated T and B cells are more resistant to MG exposure than their non-activated counterparts. In addition, other hematopoietic lineages such as natural killer cells, macrophages, and erythroid cells are quite resistant to MG-induced death. Furthermore, using various immortalized cell lines from different tissues, we found that lymphomas and thymomas are the most sensitive among all lineages tested, while epithelial cells and fibroblasts are unaffected by MG treatment. Finally, MG-induced death was shown to be independent of Fas/Fas ligand (FasL) interactions. Altogether, our findings indicate that there is a cellular specificity related to MG-mediated cell death biased towards T and B lymphocytes. This suggests that MGs could potentially be used in the treatment of specific lymphoid disorders by bypassing the requirement for the Fas/FasL system.

3T3 Cells↗

PubMed2001

Accumulation of gamma-globin mRNA and induction of erythroid differentiation after treatment of human leukaemic K562 cells with tallimustine.

Human leukaemic K562 cells can be induced in vitro to erythroid differentiation by a variety of chemical compounds, including haemin, butyric acid, 5-azacytidine, cytosine arabinoside, mithramycin and chromomycin, cisplatin and cisplatin analogues. Differentiation of K562 cells is associated with an increase of expression of embryo-fetal globin genes, such as the zeta-, epsilon- and gamma-globin genes. The K562 cell line has been proposed as a very useful in vitro model system to determine the therapeutic potential of new differentiating compounds as well as to study the molecular mechanism(s) regulating changes in the expression of embryonic and fetal human globin genes. Inducers of erythroid differentiation stimulating gamma-globin synthesis could be considered for possible use in the therapy of haematological diseases associated with a failure in the expression of normal beta-globin genes. We have analysed the effects of tallimustine and distamycin on cell growth and differentiation of K562 cells. The results demonstrated that tallimustine is a potent inducer, while distamycin is a weak inducer, of K562 cell erythroid differentiation. Erythroid differentiation was associated with an increase of accumulation of gamma-globin mRNA and of production of both haemoglobin (Hb) Gower 1 and Hb Portland. In addition, tallimustine-mediated erythroid induction occurred in the presence of activation of the apoptotic pathway. The reasons for proposing tallimustine as an inducer of gamma-globin gene expression are strongly sustained by the finding that this compound stimulates fetal haemoglobin production in human erythroid precursor cells from normal subjects.

Apoptosis↗

PubMed1988

Physiological concentrations of atrial natriuretic factor stimulate human erythroid progenitors in vitro.

Human alpha-ANF[1-28] potentiated erythroid colony formation up to four-fold in cultures containing erythropoietin. Both early and late erythroid precursor cells responded to alpha-ANF[1-28] [0.032 to 1 nM] in a dose dependent fashion. Removal of T lymphocytes and macrophages which have been shown to modulate erythropoiesis did not abolish the stimulatory effect. All major circulatory forms of ANF (alpha-ANF[1-28], alpha-ANF[4-28] and alpha-ANF[5-28]) had potent erythropoietic activity. These results indicate that concentrations of ANF reached during hypoxia stimulate erythroid progenitor cells in the presence of erythropoietin.

Atrial Natriuretic Factor↗

PubMed1987

[Somatomedin C/insulin-like growth factor I and in vitro erythropoiesis].

The effect of human somatomedin C/insulin-like growth factor I(SM-C/IGF-1) and human growth hormone (hGH) on colony formation by erythroid precursor cells (CFU-E and BFU-E) from children's bone marrow or blood was studied by methylcellulose cloning assay. We found that physiological concentrations of IGF-1, but not of hGH, stimulated erythropoiesis in vitro in the presence of erythropoietin, as demonstrated by the increased activity of a cytosolic enzyme of the heme pathway (uroporphyrinogen I synthase). The results suggest that IGF-I could be involved in the regulation of erythroid differentiation.

Bone Marrow↗

PubMedDate not supplied

[Local mechanisms of the regulatory action of Scutellaria baicalensis and ginseng extracts on the erythropoiesis after paradoxical sleep deprivation].

The influence of ginseng and skullcap (Scutellaria baicalensis) extracts on the local mechanisms of erythropoiesis control under the conditions paradoxical sleep deprivation has been studied. The regulatory action of both preparations on the bone marrow erythropoiesis is based on their ability to influence the proliferation and differentiation in erythroid cells-precursors via modulation of the functional activity of cellular hemopoiesis-inducing microenvironment elements. In particular, the drugs induce changes in the structural and functional organization of the bone marrow and in the production of short-range humoral erythropoiesis regulatory elements.

Animals↗

PubMed1995

Mechanisms of aluminum-induced microcytosis: lessons from accidental aluminum intoxication.

Twenty-three hemodialysis patients exposed to an accidental aluminum overload, showed increased erythropoietin requirements and decreased erythrocyte mean corpuscular volume (MCV). At the peak of the intoxication, MCV and plasma aluminum levels changed from unrelated (r = 0.02) to strongly related (r = 0.425) variables. The molar proportion of plasma aluminum to plasma iron increased dramatically (from 1:13.8 to 1:2.4). This significant increment in the aluminum/iron ratio made higher the relative offer of aluminum with respect to iron to the erythroid precursor cells. Accordingly, in a subset of 13 randomly selected aluminum-intoxicated patients we found increased intraerythrocytic aluminum, which paralleled the increase in plasma aluminum. Furthermore, in the aluminum-intoxicated group, intraerythrocytic ferritin, a marker of iron content, and the ratio between erythrocyte and plasma ferritin were lower (P < 0.01 and < 0.001, respectively), than in the control group. These findings support the hypothesis that in some cases of aluminum-related microcytosis, a ferropenic mycrocitosis, as expression of erythroid ferropenia, may exist in spite of the presence of normal body iron stores.

Aluminum↗

PubMed1985

Ca2+, Mg2+-dependent endonuclease activity in different subpopulations of spleen cells from normal and erythroleukemic mice.

We have detected Ca2+, Mg2+-dependent endonuclease activity in spleen cells of normal, Friend erythroleukemic, and phenylhydrazine-treated mice. When nuclei were isolated and incubated in the presence of Ca2+ and Mg2+ ions, the activity resulted in the production of 3'-OH termini in the cellular DNA and the release of chromatin due to internucleosomal DNA fragmentation. This enzyme activity was chromatin-bound and could be extracted from chromatin in an active form in 0.35 M KCl. The majority of endonuclease activity from erythroleukemic spleens was present in nuclei of precursor erythroid cells of low buoyant density (1.025-1.05 g/ml). Uninfected normal splenic tissue contained an endonuclease activity which was almost entirely confined to a B-lymphocyte population of high buoyant density (greater than 1.07 g/ml). Erythroid cell-enriched spleens from phenylhydrazine-treated mice exhibited a distribution of endonuclease activity in cells at low and high densities reflecting a mixture of erythroid and lymphoid cells. Cloned erythroleukemic cell lines propagated in vitro lacked cells of low density and showed no detectable endonuclease activity. However, nuclei from these cell lines were susceptible to exogenously added endonuclease extracted from erythroleukemic spleen cells. These same cell lines propagated as subcutaneous tumors contained endonuclease activity and a morphologically-similar low-density cell population which accounted for the endonuclease activity in these tumors. Nuclei from cloned lymphoid cell lines, representing different B-lymphocyte phenotypes, showed differences in the presence of endonuclease activity. Among the cell lines tested, only those expressing late B-cell markers showed detectable endonuclease activity.

Animals↗

PubMed2005

SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages.

The lifespan of circulating red blood cells (RBCs) produced in bone marrow is determined by their elimination through phagocytosis by splenic macrophages. The mechanism by which RBC elimination is regulated has remained unclear, however. The surface glycoprotein SHPS-1, a member of the immunoglobulin superfamily, is abundant in macrophages. We have now examined the regulation of RBC turnover with the use of mice that express a mutant form of SHPS-1 lacking most of its cytoplasmic region. The mutant mice manifested mild anemia as well as splenomegaly characterized by expansion of the red pulp. The numbers of erythroid precursor cells in the spleen and of circulating reticulocytes were also increased in the mutant mice. In contrast, the half-life of circulating RBCs was reduced in these animals, and the rate of clearance of injected opsonized RBCs from the peripheral circulation was increased in association with their incorporation into splenic macrophages. Phagocytosis of opsonized RBCs by splenic macrophages from mutant mice in vitro was also increased compared with that observed with wild-type macrophages. These results suggest that SHPS-1 negatively regulates the phagocytosis of RBCs by splenic macrophages, thereby determining both the lifespan of individual RBCs and the number of circulating erythrocytes.

Anemia↗

PubMed2004

cDNA cloning and characterization of a novel gene encoding the MLF1-interacting protein MLF1IP.

Myelodysplasia/acute myeloid leukemia (MDS/AML) is characterized by a t(3;5)(q25.1;q34) chromosomal translocation that forms a fusion gene between nucleophosmin (NPM) and MDS/myeloid leukemia factor 1 (MLF1). We identified a novel protein, MLF1-interacting protein (MLF1IP), that specifically associates with MLF1 by yeast two-hybrid analysis and in pulldown assays, and colocalizes with it in both the nuclei and cytoplasm of cells. The MLF1IP gene locus is at chromosome 4q35.1 and is composed of 14 exons spanning 75.8 kb of genomic DNA. The MLF1IP cDNA encodes a 46-kDa protein that contains two bipartite and two classical nuclear localization signals, two nuclear receptor-binding motifs (LXXLL), two leucine zippers, two PEST residues and several potential phosphorylation sites. MLF1IP transcripts are expressed in a variety of tissues (e.g. fetal liver, bone marrow, thymus and testis). MLF1IP appears to be a lineage-specific gene whose expression is confined exclusively to the CFU-E erythroid precursor cells, but not in mature erythrocytes. These observations, together with previous data demonstrating a role for MLF1 in suppressing red cell maturation, suggest a possible role for MLF1IP and MLF1 deregulation in the genesis of erythroleukemias.

Amino Acid Sequence↗

PubMed1971

Enhancement of heme and globin synthesis in cultured human marrow by certain 5 -H steroid metabolites.

These studies demonstrate that certain sex steroid metabolites are capable of significantly stimulating the synthesis of both heme and globin in cultured human bone marrow cells. These compounds, which are maximally effective at a concentration of 3 x 10(-8)M, are steroids of the C(19) and C(21) neutral type; share a common 5beta-H (A:B cis) configuration; and are derived from the in vivo biotransformation of testosterone or progesterone, or their intermediates, in man. Since these steroid metabolites have been shown to be capable in other systems of inducing the synthesis of delta-aminolevulinic acid synthetase, the limiting enzyme in the heme biosynthetic pathway, it is hypothesized that their action on human erythroid precursor cells is directed similarly at this enzymatic step leading thereby to increased heme production with consequent stimulation of globin synthesis. This steroid action is independent of erythropoietin, and since these compounds are effective at extremely low concentrations, it is suggested that they may play a physiologic role in the regulation of human erythropoiesis.

5-Aminolevulinate Synthetase↗

PubMed1999

Cathepsin A/protective protein: an unusual lysosomal multifunctional protein.

Cathepsin A/protective protein [3.4.16.5], carboxypeptidase A, is a lysosomal serine protease with structural homology to yeast (Saccharomyces cerevisiae) carboxypeptidase Y. Cathepsin A is a member of the alpha/beta hydrolase fold family and has been suggested to share a common ancestral relationship with other alpha/beta hydrolase fold enzymes, such as cholinesterases. Several lines of evidence indicate that cathepsin A is a multicatalytic enzyme with deamidase and esterase in addition to carboxypeptidase activities. Cathepsin A was recently identified in human platelets as deamidase. In vitro, it hydrolyzes a variety of bioactive peptide hormones including tachykinins, suggesting that extralysosomal cathepsin A plays a role in regulation of bioactive peptide functions. Recent reports emphasize the lysosomal protective function of cathepsin A rather than its protease function. The protective function of cathepsin A is distinct from its catalytic function. Human lysosomal beta-galactosidase and neuraminidase exist as a high molecular weight enzyme complex, in which there is a 54-kDa glycoprotein termed 'lysosomal protective protein'. Based on cell culture studies, protective protein was found to protect both beta-galactosidase and neuraminidase from intralysosomal proteolysis by forming a multienzyme complex and was shown to be deficient in patients with galactosialidosis, a combined deficiency of beta-galactosidase and neuraminidase. Molecular cloning and gene expression studies have disclosed that protective protein is cathepsin A. The cathepsin A precursor has the potential to restore both beta-galactosidase and neuraminidase activities in fibroblasts from patients with galactosialidosis. Cathepsin A knockout mice showed a phenotype similar to human galactosialidosis and the deficient phenotype found in the mutant mice was corrected by transplanting erythroid precursor cells overexpressing cathepsin A. Collectively, these findings demonstrate the significance of cathepsin A as a key molecule in the onset of galactosialidosis and also highlight the therapeutic potential of the cathepsin A precursor for patients with galactosialidosis.

Age of Onset↗

PubMedDate not supplied

Parvovirus infects cardiac myocytes in hydrops fetalis.

Parvovirus infection during pregnancy is an important cause of hydrops fetalis. It is attributed to anemia caused by viral-induced destruction of red blood cells. Infection of other organs has been reported including the heart, liver, and lungs. Few of these reports, however, convincingly demonstrate virions within the functional parenchyma of the tissue. This is of particular concern regarding myocardium in the context of hydrops fetalis which is, in part, due to cardiac failure. The problem in routine pathology practice is that most fetuses with the infection are macerated. This, in part, probably explains the paucity of published information on cardiac involvement. This study examined five cases of fatal hydrops fetalis with variable maceration with serologically proven parvovirus B19 infection. Transmission electron microscopy of cardiac tissue demonstrated intranuclear virions in both erythroid precursor cells and in cardiac myocytes in three of these cases. In each of these, immuno-gold electron microscopy provided confirmatory evidence of parvovirus infection. Virions were not identifiable where maceration had caused disintegration of nuclei in the myocytes. In addition, virions were absent in the three negative control cases where retroplacental hemorrhage was confirmed as the cause of death. This study suggests that parvovirus infection of cardiac myocytes may play a more important role in causing hydrops fetalis than previously realized. It also demonstrates that maceration should not discourage the use of electron microscopy.

Adolescent↗