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Results for “Granulocyte Precursor Cells”

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PubMedDate not supplied

[Adherence of peripheral blood neutrophils in patients with multiple sclerosis treated with ACTH. Preliminary report].

The authors studied the adherence of peripheral blood neutrophils in 15 patients with multiple sclerosis treated with ACTH. Increased adherence was found only in the whole population of white blood cells and immature precursors of granulocytes and polymorphonuclears but not in lymphocytes and eosinophils. Administration of ACTH caused a statistically not significant decrease of the adherence of various forms of white blood cells.

Adhesiveness↗

PubMed2001

Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells.

Our previous data demonstrated that cellular and nuclear tyrosine-phosphorylated Vav associate with phosphoinositide 3-kinase during all-trans-retinoic acid-dependent granulocytic differentiation of HL-60 cells. In this study, aimed to analyze the mechanism by which Vav is recruited and activated, we report that the Src homology 2 domain of Vav interacts with tyrosine-phosphorylated proteins in a differentiation-dependent manner. Two adaptor proteins, Cbl and SLP-76, were identified, showing a discrete distribution inside the cells, with Cbl absent from the nuclei and SLP-76 particularly abundant in the nuclear compartment. Of note, Vav interacts with the tyrosine kinase Syk, which is also present in the nuclear compartment and may phosphorylate Vav in vitro when cells differentiate. Inhibition of Syk activity by piceatannol prevents both in vitro and in vivo Vav tyrosine phosphorylation, its association with the regulatory subunit of phosphoinositide 3-kinase, and the nuclear modifications typically observed during granulocytic differentiation of this cell line. These findings suggest that tyrosine-phosphorylated Vav and its association with phosphoinositide 3-kinase play a crucial role in all-trans-retinoic acid-induced reorganization of the nucleoskeleton, which is responsible for the changes in nuclear morphology observed during granulocytic differentiation of HL-60 cells.

Adaptor Proteins, Signal Transducing↗

PubMed1981

Effect of tunicamycin on production by mouse fibroblast L929 cells of the factor-stimulating differentiation of mouse myeloid leukemic cells and the colony-stimulating factor.

Mouse myeloid leukemic M1 cells can be induced to differentiate into macrophages and granulocytes in vitro by a factor(s) stimulating differentiation of the cells (D-factor), which is suggested to be a glycoprotein. On the other hand, growth and differentiation of normal precursor cells of macrophages and granulocytes can be stimulated by a glycoprotein termed colony-stimulating factor (CSF). Mouse fibroblast L929 cells were found to produce both the D-factor and CSF. The properties of the D-factor and CSF and the roles of carbohydrates in the molecules of these factors were examined using tunicamycin, a specific inhibitor of asparaginase-linked glycosylation. Although both the D-factor and CSF were produced by L-cells in usual medium containing fetal calf serum, production of D-factor, but not CSF, was reduced by omission of serum from the medium. The activity of the D-factor was slightly decreased by treating the L-cells with tunicamycin (0.5 microgram/ml) in the presence of 2% fetal calf serum, without any decrease in CSF activity. Conditioned medium of L-cells incubated with or without tunicamycin was fractionated by gel filtration on a Sephadex G-200 column. Normal D-factor appeared as a single peak with an apparent molecular weight of 67,000. D-factor produced in the presence of tunicamycin had an apparent molecular weight of 25,000. On the other hand, most of the CSF was eluted in the void volume, even when it was produced in the presence of tunicamycin. The D-factor produced in the presence of tunicamycin was more sensitive than normal D-factor was to trypsin or heat treatment at 70 degrees. The CSF produced in the presence of tunicamycin was resistant to these treatments. These results indicate that the D-factor is distinct from CSF. Furthermore, the results suggest that the D-factor produced by L-cells is also a glycoprotein and that, although carbohydrate is not essential for production or activity of the D-factor, it contributes to stabilizing the protein portion of D-factor.

Animals↗

PubMed1984

Nucleolar silver-stained granules in maturing erythroid and granulocytic cells.

Human and rabbit erythroid and granulocytic precursors in bone marrow have been investigated to provide information concerning the number of nucleolar silver-stained granules (SSGs), which represent active interphasic nucleolar organizer regions (NORs). The differentiation and maturation of precursor cells of both investigated cell lines are characterized by a gradual decrease in number of nucleolar SSGs. In advanced maturation stages of erythroblasts or granulocytes, which are known to lose the capacity to divide, the number of nucleolar SSGs is smaller than the reported average or maximal values of NORs determined for human or rabbit cells. Since committed stem cells from both cell lines contain several times the number of nucleolar SSGs than the last dividing maturation and differentiation stages, the number of active parts of interphasic NORs in committed stem cells seems to be increased and might represent a stock for the later stages. In addition, the number of nucleolar SSGs appear to be a very convenient marker of nucleolar biosynthetic activity in individual differentiating and maturing blood cells. The differences between erythroid and granulocytic stem cells with respect to the number of nucleolar SSGs disappear during the course of further differentiation and maturation.

Animals↗

PubMed1989

[Studies on human basophil and eosinophil colonies in human blood mononuclear cell culture: presence of common basophil-eosinophil progenitors].

Human peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers gave rise to three types of colonies that could be distinguished by their unique morphological characteristics; 5.1 +/- 0.9 (mean +/- SE) loose colonies of small cells, 2.1 +/- 0.9 packed colonies of larger cells, and 1.6 +/- 0.7 mixed colonies, were formed when PBMC (2 x 10(5) cells/dish) from 10 healthy volunteers were cultured in the medium containing methylcellulose. Cytochemical analysis with Astra blue-eosin dual staining revealed that all types of colonies consisted of various proportions of basophils, eosinophils, and hybrid (eosinophilic and basophilic) granulocytes which contained both of granules. These hybrid granulocytes were also identified by the ultrastructural features of two kinds of the granules. Relationships between cell numbers added to culture and formed colony numbers indicated colony of the cells to form the colonies. The colonies formed from untreated patients with chronic myelogenous leukemia (CML) during chronic phase were sevenfold of those from healthy volunteers. The colonies formed from treated patients with CML were normal in number. The number was 40 times greater in culture from a patient with basophilic crisis and a patient with myeloid crisis than normal, whereas that from a patient with lymphoid crisis were within normal limit. The number of the colonies from PBMC of patients with eosinophilia were in normal range, whereas those from bone marrow were six times or more than those from PBMC. These findings suggest that PBMC contains common basophil-eosinophil progenitors, and the culture used in this study in considered to be useful in the examination of basophil and eosinophil production from PBMC. Further studies using more purified cell population and other sources of colony stimulating factors such as interleukin-3 (IL-3), IL-4, IL-5, and granulocyte-macrophage colony stimulating factor should be carried out in order to clarify the significance of hybrid granulocytes in basophil and eosinophil proliferation and differentiation.

Adult↗

PubMed1990

Megakaryocytopoiesis in experimentally induced chronic normobaric hypoxia.

It was recently proposed that prolonged hypoxia produces hypomegakaryocytic thrombocytopenia by reducing the pool of committed megakaryocyte progenitor cells at the expense of a greatly expanded erythroid progenitor pool. In order to test this hypothesis we have studied the relationship between megakaryocytopoiesis, erythropoiesis, and granulopoiesis at the level of progenitor cells (megakaryocyte colony-forming unit, CFU-Mk; erythroid CFU, CFU-E; erythroid burst-forming units; BFU-E; and granulocyte-macrophage CFU, CFU-GM) in the marrow of rats exposed for 4 weeks to normobaric hypoxia. We have found that hypomegakaryocytic thrombocytopenia was accompanied by decreased CFU-Mk, increased CFU-E, and a normal number of BFU-E and CFU-GM. These results support the hypothesis that prolonged hypoxia reduces the precursor cell commitment to differentiate into the megakaryocyte series by enhancing demand for differentiation into the erythroid cell line. However, the underlying mechanism needs further investigation.

Animals↗

PubMed2000

Flt-3 ligand, in combination with bovine granulocyte-macrophage colony-stimulating factor and interleukin-4, promotes the growth of bovine bone marrow derived dendritic cells.

Culture of bone marrow precursor cells with cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and the tyrosine kinase receptor binding proteins Flt-3 ligand (Flt-3L) and stem-cell factor (SCF), has previously been shown, in both mouse and human, to result in the generation of large numbers of dendritic cells. We extend these findings to bovine dendritic cells. Culture of bovine bone marrow cells with GM-CSF, IL-4 and either Flt-3L or SCF enhanced the generation of low buoyant-density dendritic cells. However, only the addition of Flt-3L to cells cultured with GM-CSF and IL-4 was shown to increase the number of dendritic cells and induce the differentiation of dendritic cells with potent capacity to stimulate allogeneic T cells and resting CD4+ memory T cells. The effective ability to stimulate T cells was associated with the expression of major histocompatibility complex (MHC) class II molecules and CD80/86 by dendritic cells. Bovine bone marrow derived dendritic cells appeared to be exclusively of myeloid origin because they expressed the myeloid-related antigens CD14, MyD-1 and CD11b.

Animals↗

PubMed1995

Expression of granulocyte colony-stimulating factor receptor on CD10-positive human B-cell precursors.

We examined the expression of CD10 and G-CSF receptor (G-CSFR) on the lymphoid population of mononuclear cells obtained from bone marrow (BM) using two-colour analysis. In the BM of children with ALL in remission, the CD10+ population was significantly increased (20.6 +/- 5.1% compared with that of controls (2.5 +/- 0.5%). More than half (61.3 +/- 2.9%) of the CD10+ cells co-expressed G-CSFR, but not CD13. These results indicate G-CSFR+ B-cell precursors are markedly increased in BM of ALL in remission, suggesting the probable involvement of G-CSF in the human early B-cell ontogeny.

Adolescent↗

PubMed2005

Identification of CCR2, flotillin, and gp49B genes as new G-CSF targets during neutrophilic differentiation.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that stimulates myeloid progenitor cells to proliferate and differentiate into neutrophilic granulocytes. To identify genes induced by G-CSF during neutrophil differentiation, interleukin-3-dependent murine myeloid precursor FDC-P1 cells expressing the G-CSF receptor were stimulated with G-CSF, and the gene expression profile was characterized by DNA microarray analysis. In addition to known signal transducer and activator of transcription-3 target genes, such as suppressor of cytokine signaling-3 (SOCS3), JunB, and p19(INK4D), we newly identified several G-CSF targets, including genes for the CC chemokine receptor-2 (CCR2), raft proteins flotillin-1 and flotillin-2, and immunoglobulin-like receptor gp49B. Real-time, quantitative polymerase chain reaction analyses revealed that the expression of these genes was induced in various myeloid cell lines by G-CSF. Furthermore, when HoxA9-immortalized bone marrow progenitors were induced by G-CSF to differentiate into mature neutrophils, all of these genes were strongly activated. These genes could be categorized into three groups based on their time-course of expression: immediate-early (approximately 20 min, SOCS3), mid-early (2-4 h, flotillin-1/2 and gp49B), and late (>12 h, CCR2). This suggests that different transcriptional mechanisms are involved in the regulation of these genes. We show that bone marrow neutrophils express functional CCR2, which suggest that CC chemokines may play previously unknown roles in neutrophil activation and chemotaxis.

Animals↗

PubMed1993

Unidirectional cross-phosphorylation between the granulocyte colony-stimulating factor and interleukin 3 receptors.

The mouse interleukin-3 (IL-3)-dependent hemopoietic precursor cell line 32DC13 responds to granulocyte colony-stimulating factor (G-CSF) for proliferation and differentiation. We established a subline (32D-FH) of the 32DC13 cells which has lost the ability to respond to G-CSF. When murine G-CSF receptor cDNA was introduced into the 32D-FH cell line, the transformants responded to G-CSF as well as to IL-3 for proliferation. Adding G-CSF to the transformants rapidly induced tyrosine phosphorylation not only of the G-CSF receptor but also of both subtypes of the IL-3 receptor beta-chain (AIC2A and AIC2B molecules). On the other hand, stimulation of the transformants with IL-3 induced tyrosine phosphorylation of the AIC2A and AIC2B but not of the G-CSF receptor. These results indicate that the tyrosine kinase activated through the G-CSF receptor interacts with the IL-3 receptor beta-chains but not vice versa. This unidirectional cross-phosphorylation between the G-CSF and IL-3 receptors may play a role in granulopoiesis induced by G-CSF.

Amino Acids↗

PubMed1998

CD19+ pro-B cells can give rise to dendritic cells in vitro.

Dendritic cells (DC) have the specific capacity of initiating primary T cell responses and ultimately derive from precursors in bone marrow. DC were originally thought to be only of myeloid origin, and myeloid precursor cells could be induced to differentiate into functional DC in response to granulocyte-macrophage (GM)-CSF. However, early CD4low precursor cells from the thymus can also develop into DC when cultured in IL-1beta, IL-3, IL-7, TNF-alpha, stem cell factor, and Flt-3L. In that case, GM-CSF was not required. We now show that CD19+ pro-B cells develop into DC with T cell stimulatory properties when cultured under similar conditions. These pro-B cells acquired the DC-related markers CD11c and NLDC145/DEC205, along with CD80/B7-1, CD86/B7-2, and a high density of MHC class II Ags. The marrow-derived DC did not express CD4 or CD8alpha, which are markers related to thymic DC. These findings are consistent with a new pathway through which DC are generated from B lymphoid precursors.

Animals↗

PubMed1990

Induction of the granulocyte-macrophage colony-stimulating factor (CSF) receptor by granulocyte CSF increases the differentiative options of a murine hematopoietic progenitor cell.

32DC13(G) is an interleukin-3-dependent murine hematopoietic precursor cell line which differentiates into neutrophilic granulocytes upon exposure to granulocyte colony-stimulating factor (G-CSF) but ceases to proliferate and dies when exposed to granulocyte-macrophage (GM)-CSF. Surface receptors for GM-CSF are undetectable on 32DC13(G) cells but can be induced by priming the cells with G-CSF. Exposure of the G-CSF-primed cells to GM-CSF then results in the generation of monocytes as well as granulocytes. The acquired competence to respond to GM-CSF remains irreversibly encoded in the primed cells, although the GM-CSF receptor can be down regulated by interleukin-3. This phenomenon suggests a mechanism by which hematopoietic precursors may obtain additional receptors, thereby increasing their differentiative potential.

Animals↗

PubMed1991

Plasmacytoid T-zone cell proliferation in a patient with chronic myelomonocytic leukemia. Histologic and immunohistologic characterization.

The term "plasmacytoid T-zone cells" has been used to describe distinctive cells that occur in clusters in the paracortex of some reactive lymph nodes. Recently, tumorous proliferations of these cells have been described in several patients with myelomonocytic leukemias. Neither the nature of these cells nor their relationship to myeloid leukemia has been conclusively established. We report the case of a 64-year-old woman with chronic myelomonocytic leukemia who developed lymphadenopathy that proved to be due to tumorous accumulation of plasmacytoid T-zone cells in the interfollicular regions of the lymph nodes. She underwent splenectomy because of symptomatic splenomegaly; the resected spleen also contained aggregates of plasmacytoid T-zone cells, in addition to extramedullary hematopoiesis. On treatment with busulphan and prednisone, the lymphadenopathy resolved and did not recur. The patient died 7 years later with blast transformation of her myelomonocytic leukemia and no recurrence of lymphadenopathy. The aggregates of plasmacytoid T-zone cells were architecturally and cytologically distinct from the leukemic infiltrates of myeloid cells in the spleen, and there was no evidence of differentiation of these cells into myeloid or monocytic cells. A panel of monoclonal antibodies on paraffin sections revealed no lineage-specific T- or B-cell markers (UCHL1-, L26-), and the plasmacytoid cells were positive for CD68 (KP1) and L60 (CD43), as well as faintly positive for 4KB5 (CD45RA) and MB1 (CD45R). They did not stain with antibodies to myeloid lineage antigens CD15, lysozyme, or myeloperoxidase. The combination of clinical, morphologic, and immunologic features of plasmacytoid T-zone cells in this case suggests that these cells may be of monocytic lineage but are not direct precursors of mature monocytic or granulocytic cells, and may not be part of the neoplastic clone in patients with myelomonocytic leukemia.

Antibodies, Monoclonal↗

PubMed1998

Special susceptibility to apoptosis of CD1a+ dendritic cell precursors differentiating from cord blood CD34+ progenitors.

We analyzed the effect of tumor necrosis factor (TNF)-alpha on the differentiation and viability of dendritic cells (DC) generated from cord blood CD34+ progenitors cultured for five days with GM-CSF, Flt-3 ligand (FL), and stem cell factor (SCF), and then with GM-CSF only [TNF(-) cultures]. Adding TNF-alpha from the start [TNF(+) cultures] potentiated progenitor cell proliferation and promoted early differentiation of CD1a+ DC precursors without affecting differentiation of CD14+ cells, which comprise bipotent precursors of DC and macrophages, nor of CD15+ granulocytic cells. Use of TNF-alpha was associated with increased cell mortality, which peaked on culture day 10 and mainly involved CD1a+ DC. Selective apoptosis of CD1a+ DC precursors was confirmed by showing that survival of day-7-sorted CD1a+CD14- cells from TNF(+) cultures was lower than that of CD1a-CD14+ cells. That similar findings were noted for sorted CD1a+CD14- cells of TNF(-) cultures, further cultured with GM-CSF without or with TNF-alpha, indicates that apoptosis of CD1a+ DC precursors was not induced by TNF-alpha. Apoptosis of CD1a+ DC precursors occurred after the cells had lost the capacity to incorporate bromodeoxyuridin. Finally, using higher GM-CSF concentrations or adding interleukin 3 (IL-3) improved viability of CD1a+ cells. Other cytokines, such as IL-4 and transforming growth factor (TGF)-beta1, were ineffective in this respect, though they promoted differentiation of CD1a+ DC. These results indicate that TNF-alpha promotes the differentiation of CD1a+ DC precursors, which display a high susceptibility to apoptosis that can be prevented by high concentrations of GM-CSF or use of IL-3, without affecting the differentiation of the CD14+ DC precursors.

Adult↗

PubMed1989

Interleukin-1 accelerates murine granulocyte recovery following treatment with cyclophosphamide.

This study investigated the effects of recombinant human interleukin-1 (rhIL-1 alpha) on granulocyte recovery following treatment of mice with cyclophosphamide (CPM). CF1 mice were injected with 0.5 microgram rhIL-1 alpha or heat-inactivated rhIL-1 alpha according to five different regimens, before and/or following 200 mg/kg CPM. Significant neutrophilia initially developed in treatment mice of all five regimens and accelerated granulocyte recovery occurred in treatment mice of four IL-1 regimens. Significant elevations in serum colony stimulating activity (CSA) occurred in treatment mice at a number of time points studied. In addition, marked increases in the percentage of maturing granulocyte precursors and in the proportion of cells cycling in S and G2/M were observed in treatment marrow throughout the IL-1 regimen. Before granulocyte recovery, premature nuclear segmentation was noted in metamyelocytes of treatment marrow. Concomitant with granulocyte recovery, treatment marrow was significantly more cellular and contained more total CFU-GM, more CFU-GM in S phase, more cells in S and G2/M, and more mitotic figures than control marrow. Splenic myelopoiesis was also enhanced in treatment mice. These data suggest that IL-1 significantly hastens granulocyte recovery following treatment with CPM by enhancing both proliferation and maturation of myeloid precursors.

Animals↗

PubMed1992

Comparison of in vivo and in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute myeloid leukemia.

We studied the in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in 13 patients with acute myeloid leukemia (AML) and one patient with refractory anemia with excess of blasts in transformation using the AML blast (AML colony-forming units, AML-CFU) and mixed (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) colony culture assays. In parallel, these patients received GM-CSF s.c. at 125 micrograms/m2/day, or in escalated doses starting with 10 micrograms/m2/day for a week or until circulating blast counts reached 50 x 10(9)/liter, in an effort to sensitize leukemic blasts to cell-cycle-specific agents. Results of in vivo GM-CSF treatment were correlated with those of in vitro assays. In 9 of 12 patients (75%), GM-CSF treatment increased peripheral blood blast counts (in vivo effect). GM-CSF also stimulated in vitro AML blast colony proliferation in these nine patients and increased the S+G2M phases of the cell cycle in five out of five of these patients' samples. Two of three patients in whom an in vivo response could not be demonstrated also failed to have a detectable in vitro response. These observations suggest that the AML blast colony culture assay may be useful in predicting the response of AML to cytokine therapy. Finally, GM-CSF stimulated granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) and erythroid (erythroid burst-forming units, BFU-E) colony proliferation in 14 and 11 patients, respectively, including the 3 individuals who demonstrated no clinical effect on blast counts. It is, therefore, possible that GM-CSF may be used to stimulate proliferation of progenitors that differentiate into mature granulocyte, monocyte-macrophage, and erythroid cells.

Acute Disease↗

PubMed1988

Characterization of granulocytes and mast cells in cultures of mouse bone marrow stimulated with interleukin-3.

Bone marrow cells in liquid culture with interleukin 3 produce a population of non-adherent granulocytes and mast cells. Flow cytometry was used to identify granulocytes and mast cells on the basis of the physical properties of perpendicular light scatter (PLS) and coulter volume (CV) as well as the expression IgE and CR3 receptors. Multicolor analysis indicated there were subpopulations of Thy1.2 positive cells which transiently appeared in these cultures and also expressed IgE receptors, CR3 receptors or neither of these receptors. The data suggested a differentiation scheme in which Thy1.2 positive precursor cells give rise to granulocytes and mast cells. Further evidence for this differentiation scheme was provided from CV vs. PLS distributions which showed increases in CV and PLS as Thy1.2 positive cells differentiated into mast cells and decreases in CV and PLS as Thy1.2 positive cells differentiated into granulocytes.

Animals↗

PubMed1994

Haemopoietic colony-forming cells from peripheral blood stem cell harvests: cytokine requirements and lineage potential.

We have measured the in vitro growth requirements of progenitor cells released into the blood of cancer patients following administration of chemotherapy and cytokines. In order to distinguish the direct effects of cytokines on progenitors from those activating accessory cells, we have compared clonogenic growth before and after CD34-positive selection of progenitors, in serum-free conditions. CD34 selection had little effect on the cytokine requirements of erythroid colony-forming cells and single cytokines, particularly interleukin-3, could support considerable colony growth in both mononuclear and CD34+ cell suspensions. Optimal erythroid colony growth, however, usually required the addition of a combination of stem cell factor and interleukin-3, in addition to erythropoietin, which was always required. Maximal numbers of granulocyte-monocyte progenitors in mononuclear cell cultures, could be achieved with a mixture of stem cell factor, interleukin-3 and granulocyte-monocyte colony stimulating factor. However, after CD34 selection, full myeloid colony growth was only achieved when granulocyte colony stimulating factor was added to the above mixture. This presumably reflects loss of accessory cells, during CD34 selection, which produce this cytokine. When transplanted after 8 d of culture, 16/22 myeloid colonies from erythropoietin-free cultures of peripheral blood stem cell harvests, could generate secondary erythroid colonies implying that these progenitors are multipotential. However, surface marker analysis of individual erythroid colonies revealed only the occasional presence of granulocytes and monocytes. These data demonstrate that cytokine mixtures are required for optimal colony growth, particularly after CD34 selection, and that most mobilized, blood clonogenic cells are multipotential.

Antigens, CD↗