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Results for “Granulocyte Precursor Cells”

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PubMed1984

Antigenic analysis of hematopoiesis: II. Expression of human neutrophil antigens on normal and leukemic marrow cells.

The binding of five antineutrophil monoclonal antibodies AHN-1, -2, -3, -7, and -8, to normal and leukemic bone marrow cells was studied. AHN-7 bound to many granulocytic precursors, particularly myelocytes, and both lymphoid and blast cells in normal marrow, and to most but not all granulocyte-macrophage progenitors (CFC-GM). AHN-8 bound only to late (band and segmented) neutrophilic cells and not to CFC-GM. AHN-1, -2, -3 bound to morphologically identifiable neutrophil precursors, but not to (day-14) CFC-GM. Approximately half of nonlymphoid leukemia specimens were positive with AHN-1 or AHN-7; by contrast, lymphoid leukemia specimens were rarely positive. AHN-8 was rarely found on leukemic cells. These antineutrophil antibodies appear to detect distinct granulopoietic subsets and may be useful in the analysis of hematologic differentiation and in the subclassification of leukemias.

Animals↗

PubMed1994

Extramedullary haemopoiesis in fetal and adult human spleen: a quantitative immunohistological study.

Haemopoietic cells were assessed in spleens from normal adults, adults with splenic extramedullary haemopoiesis due to chronic myeloproliferative disorders and fetuses of 17-21 weeks' gestation. A variety of antigens expressed by developing granulocytes and erythrocytes were demonstrated immunohistochemically. The relative proportions of early and late precursor cells of these two lineages were quantified. There was no significant haemopoiesis in normal adult spleen, while there was abundant (predominantly granulocytic) haemopoiesis in patients with chronic myeloproliferative disorders. Fetal spleens contained numerous late erythroid precursors but few early erythroid or granulocytic cells. The relative numbers of early and late haemopoietic cells in adult chronic myeloproliferative disorders and fetal spleens showed statistically significant differences. Our findings indicate that haemopoiesis in the spleens of adult patients with these disorders differs fundamentally from that occurring in fetal life. They support the view that the human spleen does not have a significant role in fetal haemopoiesis, but that it filters circulating nucleated erythroid precursors and is permissive of their terminal differentiation only. Our results also favour the view that adult splenic haemopoiesis originates by displacement of precursor cells from the bone marrow rather than by activation of stem cells which have lain dormant in the spleen since fetal life.

Adult↗

PubMed1982

Autologous bone marrow rescue in the treatment of advanced tumors of childhood.

High-dose multiagent chemotherapy followed by autologous marrow rescue was used in the treatment of 13 patients with Stage III or IV childhood tumors. Encouraging results are being obtained in abdominal lymphoma (1/3 complete remissions (CR); rhabdomyosarcoma (2/4 CR); and retinoblastoma (1/2 CR). In neuroblastoma, the results are disappointing, with only one of four patients in CR; this patient developed a lymphoma associated with Epstein-Barr virus infection. Marrow reconstitution was obtained in 11 patients, with recovery of neutrophils to greater than 0.5 x 10(9)/liter between six and 30 days and platelet recovery to greater than 50 x 10(9)/liter between seven and 38 days. Investigations on the numbers of cells or committed granulocyte precursors ()CFU-c's) infused and parameters of hematologic recovery show poor correlation and suggest that a more accurate and reliable assay for the predictability of cryopreserved marrow to reconstitute marrow function within a reasonable time is necessary. Nonhematologic toxicities of high-dose multiagent chemotherapy are the principal dose-limiting factors.

Adolescent↗

PubMed2000

Definition of human blood monocytes.

At the Definition of Human Blood Monocytes conference held in Munich, Germany in October 1999, experts met to discuss data on the characterization of monocytes in health and disease. Emphasis was on how to best define these cells, on which subpopulations can be identified, and on how the monocytes can best be distinguished from other cells such as natural killer cells, granulocytes, and dendritic cell precursors.

Antigens, CD↗

PubMed1983

Myeloproliferative Sarcoma Virus stimulates pluripotent hematopoietic stem cells and provokes tumoral transformation of the hematopoietic microenvironment in vitro.

The Myeloproliferative Sarcoma Virus (MPSV) induces an increase in the number and concentration of pluripotent stem cells in long-term murine bone marrow cultures. This is followed by an increased number of precursor cells of the granulocyte and macrophage lines (GM-CFC). This increase is comparable to that observed in DBA/2 mouse spleens in vivo two to three weeks after viral infection. Proliferation of CFUs and GM-CFC decreases five weeks after infection with MPSV, in parallel to the gradual decline of reverse transcriptase activity in the culture medium. GM-CFC which can proliferate in the absence of added colony stimulating factor (CSF) were detected at week 6 post MPSV infection. Adherent tumor cells were observed nine weeks after infection. These fibroblast type cells gave rise to a permanent line which produced a CSF-like activity. Our results show that MPSV causes the tumoral transformation of fibroblast-like cells of the bone-marrow hematopoietic microenvironment. In addition, MPSV also strongly stimulates the proliferation of hematopoietic stem cells. MPSV is, until now, the first murine retrovirus which exhibits such properties.

Animals↗

PubMed2004

Intracerebellar granulocytic sarcoma complicating acute myelogenous leukemia: a case report and review of the literature.

Granulocytic sarcoma is a solid mass composed of premature precursors of granulocytic series cells in an extramedullary region. Intraparenchymal central nervous system localization without skull or meningeal invasion is extremely rare. Although different theories have been proposed to explain the mechanism of this unusual disorder, its exact mechanism is still unclear. Some degree of improvement can be achieved after surgery and radiotherapy but its prognosis is poor and most patients die within months. Nine cases of purely intraparenchymal granulocytic sarcomas have been reported in the literature. Here, we report the tenth case and review the current literature.

Cerebellar Neoplasms↗

PubMed1979

Colony-stimulating factor (CSF) radioimmunoassay: detection of a CSF subclass stimulating macrophage production.

Colony-stimulating factors (CSFs) stimulate the differentiation of immature precursor cells to mature granulocytes and macrophages. Purified 125I-labeled murine L cell CSF has been used to develop a radioimmunoassay (RIA) that detects a subclass of CSFs that stimulates macrophage production. Murine CSF preparations that contain this subclass of CSF complete for all of the CSF binding sites on anti-L cell CSF antibody. With the exception of mouse serum, which can contain inhibitors of the bioassay, there is complete correspondence between activities determined by RIA and those determined by bioassay. The RIA is slightly more sensitive than the bioassay, detecting approximately 0.3 fmol of purified L cell CSF. It also detect this subclass of CSF in chickens, rats, and humans. In the mouse, the subclass is distinguished from other CSFs by a murine cell bioassay dose-response curve in which 90% of the response occurs over a 10-fold (rather than a 100-fold) increase in concentration, by stimulating the formation of colonies containing a high proportion of mononuclear (rather than granulocytic) cells, and by certain physical characteristics.

Animals↗

PubMed1985

Cloning, sequence, and expression of a human granulocyte/macrophage colony-stimulating factor.

Human granulocyte/macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that is essential for the in vitro proliferation and differentiation of precursor cells into mature granulocytes and macrophages. In this report we have used a mouse GM-CSF cDNA clone to isolate human GM-CSF clones from libraries made from HUT-102 messenger RNA and mitogen-stimulated T-lymphocyte messenger RNA. The human cDNA clones contained a single open-reading frame encoding a protein of 144 amino acids with a predicted molecular mass of 16,293 daltons and showed 69% nucleotide homology and 54% amino acid homology to mouse GM-CSF. One of these cDNA clones was shown to direct the synthesis of biologically active GM-CSF using a yeast expression system. The gene for human GM-CSF appears to exist as a single-copy gene.

Amino Acid Sequence↗

PubMed1975

Kinetic-microarchitectural correlations in the bone marrow of the mouse.

Transverse histologic sections of bone marrow obtained from mice that were sacrificed by perfusion fixation at intervals following tritiated thymidine injection were studied by means of radioautography. A kinetic gradient was demonstrated across the marrow section, with the highest proliferative rate in the subendosteal region. Megakaryocytes were shown to originate from the rapidly proliferating subendosteal cells. The immediate proliferating precursors of mature granulocytes were slowly proliferating cells found predominantly in the central region of the marrow. It was concluded that in the steady state there must be a migration of cells from the subendosteal region to the central region with concomitant growth retardation of the migrating cells.

Animals↗

PubMed1989

Interferon beta 2/interleukin 6 modulates synthesis of alpha 1-antitrypsin in human mononuclear phagocytes and in human hepatoma cells.

The cytokine IFN beta 2/IL-6 has recently been shown to regulate the expression of genes encoding hepatic acute phase plasma proteins. INF beta 2/IL-6 has also been shown to be identical to MGI-2, a protein that induces differentiation of bone marrow precursor cells toward mature granulocytes and monocytes. Accordingly, we have examined the effect of IFN beta 2/IL-6 on expression of the IL-1- and tumor necrosis factor-unresponsive acute phase protein alpha 1-antitrypsin (alpha 1 AT) in human hepatoma-derived hepatocytes and in human mononuclear phagocytes. Purified human fibroblast and recombinant IFN beta 2/IL-6 each mediate a specific increase in steady-state levels of alpha 1 AT mRNA and a corresponding increase in net synthesis of alpha 1 AT in primary cultures of human peripheral blood monocytes as well as in HepG2 and Hep3B cells. Thus, the effect of IFN beta 2/IL-6 on alpha 1 AT gene expression in these cells is primarily due to an increase in accumulation of alpha 1 AT mRNA and can be distinguished from the direct, predominantly translational effect of bacterial lipopolysaccharide on expression of this gene in monocytes and macrophages. The results indicate that IFN beta 2/IL-6 regulates acute phase gene expression, specifically alpha 1 AT gene expression, in extrahepatic as well as hepatic cell types.

Carcinoma, Hepatocellular↗

PubMed2000

Lentiviral vector transduction of hematopoietic stem cells that mediate long-term reconstitution of lethally irradiated mice.

Lentiviral vectors efficiently transduce human CD34(+) cells that mediate long-term engraftment of nonobese diabetic/severe combined immunodeficient mice. However, hematopoiesis in these animals is abnormal. Typically, 95% of the human cells in peripheral blood are B lymphocytes. To determine whether lentiviral vectors efficiently transduce stem cells that maintain normal hematopoiesis in vivo, we isolated Sca-1(+)c-Kit(+)Lin(-) bone marrow cells from mice without 5-fluorouracil treatment, and transduced these cells in the absence of cytokine stimulation with a novel lentiviral vector containing a GFP (green flourescent protein) reporter gene. These cells were transplanted into lethally irradiated C57Bl/6 mice. In fully reconstituted animals, GFP expression was observed in 8.0% of peripheral blood mononuclear cells for 20 weeks posttransplantation. Lineage analysis demonstrated that a similar percentage (approximately 8.0%) of GFP-positive cells was detected in peripheral blood B cells, T cells, granulocytes and monocytes, bone marrow erythroid precursor cells, splenic B cells, and thymic T cells. In secondary transplant recipients, up to 20% of some lineages expressed GFP. Our results suggest that quiescent, hematopoietic stem cells are efficiently transduced by lentiviral vectors without impairing self-renewal and normal lineage specification in vivo. Efficient gene delivery into murine stem cells with lentiviral vectors will allow direct tests of genetic therapies in mouse models of hematopoietic diseases such as sickle cell anemia and thalassemia, in which corrected cells may have a selective survival advantage.

Animals↗

PubMed2001

Il-17 mobilizes peripheral blood stem cells with short- and long-term repopulating ability in mice.

Autologous and allogeneic bone marrow transplantations have evolved as important cancer therapy modalities. For both indications, peripheral blood has been shown to have distinct advantages over bone marrow as the stem cell source. Cytokine combinations for mobilization have enhanced stem cell yield and accelerated engraftment. However, novel mobilizing agents and strategies are needed to further improve clinical outcomes. Within the donor graft, the dynamic equilibrium between T cells and stem cells critically influences engraftment and transplantation results. IL-17 is a cytokine produced almost exclusively from activated T cells. IL-17 was expressed in vivo with adenovirus technology. Here, proof-of-principle studies demonstrate that IL-17 effectively mobilizes hemopoietic precursor cells (CFU-granulocyte-erythrocyte-macrophage-monocyte, CFU-high proliferative potential) and primitive hemopoietic stem cells (Lin(-/low)c-kit(+)Sca1(+)). Moreover, mouse IL-17 adenovirus-mobilized peripheral blood stem cells rescued lethally irradiated mice. Bone marrow was found to be 45-75% of donor origin at 1 year. In secondary recipients, donor-derived bone marrow cells ranged from 45 to 95%. These data show that IL-17 mobilizes stem cells in mice with short- and long-term reconstituting capacity. Additional comparative studies are needed as well as studies in tumor models to refine distinct potential clinical applications for IL-17-mobilized peripheral blood stem cells.

Animals↗

PubMed1991

[A histopathological study of bone marrow in acute myeloid leukemia. Bone marrow biopsy changes before chemotherapy and comparison with bone marrow smears].

Histopathological changes of pretreatment bone marrow biopsy from 42 cases with acute myeloid leukemia (AML) were described. A considerable difference was shown between the results of aspirate smears and the findings of plastic embedded biopsy sections, particularly in bone marrow cellularity such as infiltration of inflammatory cells and presence of residual hemopoietic cells, qualitative and quantitative abnormalities of megakaryocytes suggestive of myelodysplastic features were more accurately assessed in the sections of marrow biopsy than in the aspirate smears. In three cases there was considerable infiltration of maturing but dysplastic granulocytic cells and erythroid precursors in the sections, but not in the aspirate smears. Our study shows that plastic embedded biopsy sections provide more information than aspiration smears for the diagnosis of AML.

Adolescent↗

PubMed2005

Neurosis-associated changes in the granulocytic hemopoietic stem in mice with different learning capacity.

We studied the local mechanisms of neurosis-associated changes in the granulocytic hemopoietic stem in CBA/CaLac mice with different learning capacity. It was found that in good learners hyperplasia of the bone marrow granulocytopoiesis during neurosis was related to enhanced proliferative activity and accelerated maturation of granulocyte-macrophage precursors resulting from increased formation of granulocytic and erythrogranulocytic hemopoietic islets. In poor learners primary suppression of the bone marrow granulocytopoiesis was associated with impaired formation of hemopoietic islets (conflict situation) and inhibition of differentiation of granulocyte-macrophage precursors (paradoxical sleep deprivation followed by T-maze learning). Then, recovered ability of bone marrow cells to form granulocyte complexes even against the background of inhibition of precursor differentiation (conflict situation) and accelerated maturation of granulocytic cells (paradoxical sleep deprivation and maze learning) lead to hyperplasia of the granulocytic hemopoietic stem.

Animals↗

PubMed2005

Effect of granulocyte colony-stimulating factor on kinetics of hemopoietic precursors in regenerating bone marrow.

We studied processes of proliferation and differentiation of hemopoietic precursor cells in mice treated with granulocyte CSF under conditions of cytostatic myelodepression. It was found that the hemostimulating effect of original granulocyte CSF preparation consists in accelerated maturation of hemopoietic precursors and increased content of DNA-synthesizing CFU-GM in the bone marrow.

Animals↗

PubMed1989

Leucopoiesis versus concentration of cytokines in diffusion chamber cultures of mouse bone marrow cells: clues to the physiological roles of growth factors.

Physiological mechanisms that regulate formation of neutrophil granulocytes, macrophages and their precursor cells were studied with the diffusion chamber (DC) technique. DC inoculated with mouse bone marrow cells were implanted intraperitoneally into host mice. When these in vivo cultures had been established and their marrow populations were expanding (2-day cultures), the DC were transferred to different environments: new, normal mice, lethally irradiated mice, or incubation flasks with optimal concentrations of growth factors. Culture development during the following final culture period was correlated to the concentration of some select candidate growth regulators in DC. After 3 d the cellularity of DC in irradiated hosts had increased significantly more than in the normal hosts. A difference was detectable already after 1-2 d when preculturing was omitted. The increased growth appeared to take place at several stages of cell maturation and not only at the progenitor cell level. Colony stimulating factor(s) for granulocyte and macrophage progenitors, as well as cytokines stimulating the bone marrow-derived cell line, 14 M.1, were present in DC fluid (DCF) at higher concentrations in irradiated than in normal mice throughout the final culture period. On the other hand, DCF concentrations of tumour necrosis-like factor (that may either induce CSF secretion or directly inhibit myelopoiesis), were not significantly different in irradiated compared with normal DC hosts. The cytokines detected in the DC may at least in part stem from inflammatory cells accumulating around the chambers. This animal model should be useful in further investigation of the highly complex regulatory network governing formation of white blood cells in the intact organism.

Animals↗

PubMedDate not supplied

[The infection of mice with the influenza virus suppresses bone marrow precursor differentiation in the erythroid and granulocyte directions].

Mice (CBA X C57BL/6)F1 were inoculated intranasally with nonlethal doses of influenza A/PR/8/34 virus (500 EID50). At different intervals postinoculation, bone marrow cells were collected from them and inoculated intravenously to lethally irradiated syngeneic recipients with the purpose of determination of the histological types of colony-forming units of spleen (CFUs). On day 3 after inoculation, inhibition of CFUs differentiation in erythroid and granulocytic directions was observed, and in 7 days only granulocytic shoot of hemopoiesis was inhibited. Lymph node cells of the donors in 3 days postinoculation inhibited the colony-forming activity of bone marrow cells of intact mice with suppression of differentiation of erythrocytes and granulocytes. The possible mechanisms of influenza virus-mediated effect on the processes of bone marrow hemopoiesis are discussed.

Animals↗

PubMed1981

Characterization of macrophage- and granulocyte-inducing proteins for normal and leukemic myeloid cells produced by the Krebs ascites tumor.

Medium from serum-free cultures of Krebs ascites tumor cells contains two macrophage and granulocyte inducing (MGI) activities that can act on the myeloid precursors of these hematopoietic cells. One activity, MGI-1, induced the formation of macrophage and granulocyte colonies from normal myeloid precursors. The second activity, MGI-2, induced macrophage and granulocyte differentiation in myeloid leukemic cells that no longer required MGI-1 for colony formation. The medium contained one species of MGI-1 and two species of MGI-2. One species of MGI-2, MGI-2A, copurified through five stages of purification with MGI-1, but separated from the other MGI-2 species, MGI-2B, at an early stage in purification. MGI-1, MGI-2A and MGI-2B were purified 1490, 1140 and 678-fold, respectively. When bands with biological activity gel from non-denaturing polyacrylamide gels were run on SDS-polyacrylamide gel electrophoresis, MGI-1 and MGI-2A activities were associated with similar Mr and each activity showed two bands, one of 23 000 and the other 25 000. MGI-2B activity showed one band with a Mr of 45 000. Secretion did not appear to involve glycosylation, none of the species bound to concanavalin A, soybean agglutinin, or wheat germ agglutinin agarose columns and they did not appear to contain carbohydrates. The assays for MGI-1 and MGI-2 activities were not affected by adding protease inhibitors. But MGI-2 was more readily destroyed by treatment with proteases and was more labile at high temperature and low pH than MGI-1. It is suggested that the level of cellular proteases may play a role in regulating the relative amounts of MGI-1 and MGI-2 that are present in vivo.

Animals↗