PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Granulocyte Precursor Cells”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 127 records · Page 7Linked to original sources

[Granulocytic sarcoma (chloroma) in ophthalmology].

Granulocytic sarcoma (chloroma) is a tumor composed of granulocytic precursor cells, preceding or more often occurring during the course of myelogenous leukemia. Three ophthalmic localisations, two in the orbit and one in the uvea, are reported, two cases concerning young adults (29 years) and the third a 10-year-old boy. In all three cases, the tumor preceded the hematologic disease (18 months in the first case, 10 months in the second case, 2 years in the third case). In such cases (when the tumor becomes clinically apparent before the leukemia) diagnosis is often very difficult but can be assisted by studying the morphology of the cells, which show occasional eosinophilic myelocytes. Histochemical staining for esterase activity (Naphtol A.S.D. Chloracetate stain) has greatly improved the ability to make a histopathologic diagnosis before the hematologic manifestations.

Adult↗

Autoimmune neutropenia.

There have been several new developments in the field of autoimmune neutropenia over the past decade. Neutropenia caused by antibodies directed against granulocyte precursor cells, the oligoclonal nature of antineutrophil antibodies, and the expanding knowledge of neutrophil antigens, particularly in relationship to autoantibodies, are exciting new areas of investigation. Knowledge has also been advanced in the effector mechanisms of neutrophil autoantibodies and the effect of autoantibodies on the neutrophil function. In addition, some clinical syndromes of immune neutropenia have been better defined over the past decade, such as autoimmune neutropenia of infancy and chronic idiopathic neutropenia in adults. The past decade also saw interesting developments in the treatment of immune neutropenia, particularly in the use of gammaglobulin preparations and more recently in the advent of hematopoietic growth factors. This review focuses on these newer aspects of autoimmune neutropenia.

Animals↗

Phenotypes and phosphatidylinositol glycan-class A gene abnormalities during cell differentiation and maturation from precursor cells to mature granulocytes in patients with paroxysmal nocturnal hemoglobinuria.

To define the phosphatidylinositol glycan-class A (PIG-A) gene abnormality in precursor cells and the changes of expression of glycosylphosphatidylinositol-anchored protein and contribution of paroxysmal nocturnal hemoglobinuria (PNH) clones with PIG-A gene abnormalities among various cell lineages during differentiation and maturation, we investigated CD59 expression on bone marrow CD34(+) cells and peripheral granulocytes from 3 patients with PNH and the PIG-A gene abnormalities in the CD59(-), CD59(+/-), and CD59(+) populations by nucleotide sequence analyses. We also performed clonogeneic assays of CD34(+)CD59(+) and CD34(+)CD59(-) cells from 2 of the patients and examined the PIG-A gene abnormalities in the cultured cells. In case 1, the CD34(+) cells and granulocytes consisted of CD59(-) and CD59(+) populations and CD59(-), CD59(+/-), and CD59(+) populations, respectively. Sequence analyses indicated that mutation 1-2 was in the CD59(+/-) granulocyte population (20 of 20) and the CD34(+)CD59(-) population (2 of 38). In cases 2 and 3, the CD34(+) cells and granulocytes consisted of CD59(+) and CD59(-) cells. Sequence analyses in case 3 showed that mutation 3-2 was not in CD34(+)CD59(-) cells and was present in the CD59(-) granulocyte population. However, PIG-A gene analysis of cultured CD34(+)CD59(-) cells showed that they had the mutation. This analysis also revealed that there were some other mutations, which were not found in CD34(+)CD59(-) cells and CD59(-) or CD59(+/-) granulocytes in vivo, and that sometimes they were distributed specifically among different cell lineages. In conclusion, our findings suggest that PNH clones might contribute qualitatively and quantitatively differentially to specific blood cell lineages during differentiation and maturation of hematopoietic stem cells.

Aged↗

Isolation of pluripotent hemopoietic stem cells and clonable precursor cells of erythrocytes, granulocytes, macrophages and megakaryocytes from mouse bone marrow.

Murine pluripotent hematopoietic stem cells and precursor cells with restricted commitment to erythrocytes, granulocytes and macrophages as well as megakaryocytes have been purified 30- to 50-fold from mouse bone marrow cells. Purification was achieved by a three-step procedure. Bone marrow cell populations free of erythroid cells and lymphocytes were obtained by culturing the cells for several weeks. Macrophages and adherent polymorphic neutrophils (PMN) were removed by adherence to plastic. The remainder of the PMN along with more primitive granulocytes (but not promyelocytes and some monocytoid cells) were removed either by neutral density centrifugation or by differential centrifugation after rosette formation with sheep erythrocytes coated with immunoglobulin (EA rosettes). The remaining population of marrow-derived cells contained 40-66% blast cells, 20-35% promyelocytes and 5-10% other cells (usually PMNs and monocytes). Using cloning techniques to detect immature hemopoietic cells, this population contained 15-35% granulocyte-macrophage progenitor cells, approximately 0.2% erythroid burst-forming cells, approximately 0.1% megakaryocyte progenitor cells and 1-3% pluripotent stem cells (based on seeding efficiency 0.06).

Animals↗

The effect of 5-aminolevulinic acid-based photodynamic treatment (PDT) on nucleoli of leukemic granulocytic precursors represented by K562 blastic cells in vitro.

BACKGROUND: Since photodynamic treatment (PDT) induces apoptosis in individual HL-60 cells originating from early granulocytic precursors of acute myeloid leukemia, the present study was undertaken to provide information on such treatment of K562 cells, which originate from early granulocytic precursors of chronic myeloid leukemia (blastic phase) and carry the bcr/abl fusion gene with anti-apoptotic properties. MATERIAL/METHODS: PDT was based on the 5-aminolevulinic acid treatment of K562 cells, followed by blue light irradiation under conditions which in HL-60 cells induce an apoptotic process without previous terminal maturation. Nuclei and nucleoli were visualized by cytochemical procedures to demonstrate DNA, RNA and silver stained proteins of nucleolus organizer regions (AgNORs). TUNEL and propidium iodide assays were used for additional control of the incidence of apoptotic and necrotic cells. RESULTS: In contrast to HL-60 cells, PDT did not induce apoptosis in K562 cells. However, after PDT some K562 cells exhibited major alterations, expressed by nuclear and cell swelling, reflecting a necrotic process, confirmed by propidium iodide. In addition, PDT produced a reduction of AgNORs, though smaller than that previously described in apoptotic HL-60 cells. CONCLUSIONS: PDT produced only necrotic changes in some K562 cells under conditions which induced in apoptosis in HL-60 cells. Thus the induction of apoptosis, nuclear and nucleolar changes in individual cells does not depend on the inducer--PDT--but on the cell properties.

Aminolevulinic Acid↗

Granulocyte precursors are the principal cells in bone marrow that stimulate allospecific cytolytic T-lymphocyte responses.

Mouse bone marrow cells were fractionated and enriched for functional activity as stimulators of allospecific cytolytic T-lymphocyte (CTL) responses in vitro. The relevant stimulator cells were enriched sequentially in the low-density fraction of bone marrow, its 2-hr adherent and 18-hr non-adherent fractions and in the FcR-negative fraction of 18-hr non-adherent cells. The functionally enriched cell population contained over 90% granulocyte precursors by ultrastructural analysis. The results indicate that granulocyte precursors are the principal cells in bone marrow that stimulate alloreactive T-cell responses.

Animals↗

Changes in the surface morphologies of the cells in the bursa cloacalis (bursa of Fabricius) and thymus during ontogeny of the chick embryo.

Slices or sections through the bursa cloacalis and thymus of chick embryos at 7-21 days of incubation were observed by light and electron microscopy to determine whether major differences existed in the surface morphologies of lymphoid cells in these organs, and whether the surface morphologies of these cells changed during ontogeny. These organs were fixed concurrently and identically at each stage. The thymus was packed at all stages with spherical cells having fine structures characteristic of those of lymphoid cells. Many irregularly shaped, epithelial cell processes were present between lymphoid cells. The bursa contained many irregularly shaped stromal cells as well as spherical cells. The latter were few in number during early development, but became the predominant type of cell near the end of incubation. Spherical cells in the bursa consisted of three types based on fine structure: lymphoid cells, granulocytic cells, and cells which were probably precursors of granulocytic cells. Spherical cells in the bursa could not be classified into these three types by their surface morphologies, however, because the latter at any one stage of development were similar. At 7-8 days of incubation, spherical cells in the bursa could not be differentiated consistently from neighboring stromal cells by scanning electron microscopy alone, but by 9 days, spherical cells could be identified routinely by this method. At 9-10 days of incubation, only minor differences existed in the surface morphologies of the spherical cells in the bursa and thymus: Bursal cells displayed long, ridgelike processes, whereas thymic cells exhibited fine surface undulations and large blebs. At 11 days, the surfaces of the spherical cells in the bursa were covered by numerous short microvilli, but the surfaces of thymic cells were unchanged. Bursal cells retained their microvilli through 14 days of incubation, but between 15 and 21 days progressively lost their microvilli, becoming essentially bald near the end of this period. Likewise, thymic cells gradually lost their surface wrinkles and blebs. Near the time of hatching, both types of cells were smooth-surfaced and tightly packed, with individual cells assuming polyhedral configurations.

Animals↗

Homing efficiency and hematopoietic reconstitution of bone marrow-derived stroma cells expanded by recombinant human macrophage-colony stimulating factor in vitro.

The increasing recognition of the properties of marrow stromal cells has spawned a major switch in our perception of their nature and the potential therapeutic applications that have been envisioned and implemented. Yet, several aspects of bone marrow stromal cell biology remain in question. This report describes the ability of recombinant human macrophage colony-stimulating factor (rhM-CSF) to maintain proliferation and differentiation of bone marrow stromal cells ex vivo. Our results demonstrated that M-CSF was essential for proliferation and differentiation of bone marrow-derived stromal cells and exerted its effects in a dose-dependent manner. The number of colony-forming unit (CFU) fibroblasts increased by 25% after incubation with rhM-CSF. In vitro expanded bone marrow stromal cells were easy to passage and differentiated to adipocyte and chondroblast cells under appropriate culture conditions. Furthermore, these expanded stromal cells to support CD34+ hematopoietic stem cells, as demonstrated by their ability to form CFU-Mix, burst-forming units-erythroid, and CFU-granulocyte macrophage colonies after 3 weeks of culture. The homing efficiency of in vitro expanded or fresh isolated bone marrow-derived stromal cells, which were labeled with carboxy fluorescein diacetate succinimidyl ester, to bone marrow was also investigated. Homing assays demonstrated that freshly isolated CD45+-depleted bone marrow cells were able to home to bone marrow in a dose-dependent manner, although some cells were found in the spleen, liver, and lung. However, their ability to home was dramatically reduced with culture time and was completely lost after five to seven passages in vitro. Animal studies showed that freshly isolated or rhM-CSF-induced bone marrow stromal cells promoted hematopoietic reconstitution in lethally irradiated mice. The ability to easily expand human stromal cells, which support survival and proliferation of CD34+ cells, has many important clinical applications for hematopoietic disorders.

Adipocytes↗

Immunophenotypic differentiation patterns of normal hematopoiesis in human bone marrow: reference patterns for age-related changes and disease-induced shifts.

BACKGROUND: The abundance of monoclonal antibodies (mAb) and the routine use of quadruple stainings in flow cytometry allow stepwise analysis of bone marrow (BM) samples that are suspected for abnormal hematopoiesis. A screening phase that precedes lineage-specific classification phases should be sufficient to assess whether the BM has a normal or abnormal composition, as well as to identify the abnormal differentiation lineage. METHODS: For a quick and easy flow cytometric screening of BM samples, we selected six quadruple immunostainings that cover multiple differentiation stages of the B-cell, monocytic, granulocytic, and erythroid lineages: TdT/CD20/CD19/CD10 and CD45/CD34/CD19/CD22 for B cells, CD34/CD117/CD45/CD13.33 for precursor granulocytic and precursor monocytic cells (myelo/monoblasts), CD14/CD33/CD45/CD34 for monocytic cells, CD16/CD13/CD45/CD11b for granulocytic cells, and CD71/CD235a/CD45/CD117 for erythroid cells. RESULTS: The six quadruple immunostainings reveal specific staining patterns in normal BM, which allow the recognition of various subpopulations of the respective lineages. These staining patterns can be used as a frame of reference for recognition of normal and abnormal BM development. Examples of normal (age-related) variations in these otherwise stable staining patterns are presented together with several abnormal differentiation patterns. CONCLUSIONS: Although alternative immunostainings can be used (e.g., including NK- and T-cell markers), we feel that the selected six stainings represent a comprehensive and easy screening phase for quick identification of shifts in the composition of the studied differentiation lineages, reflecting age-related changes or disease-induced BM abnormalities.

Aging↗

An in vitro study on the mechanisms of coagulation activation in acute myelogenous leukemia (AML): role of tissue factor regulation by cytotoxic drugs and GM-CSF.

AML patients may suffer from a disseminated coagulopathy, which can aggravate a pre-existing bleeding tendency due to thrombocytopenia and platelet dysfunction. The cellular and molecular mechanisms underlying this coagulopathy, however, are not completely understood. Indeed, the broad and increasing therapeutic use of cytotoxic drugs and growth factors is likely to contribute to the complexity of hemostatic abnormalities encountered in this hematologic malignancy. The nature of coagulation activation in AML was therefore investigated in vitro using the human leukemic cell line, HL60. Tissue factor (TF) was almost entirely located on the cell surface and bound factor VIIa, but only 15-25% of this TF was primarily functionally active. Treatment with increasing concentrations of daunorubicin or cytosine-beta-D-arabinofuranoside, two cytotoxic drugs commonly used in AML therapy, induced apoptosis and secondary necrosis of HL60 cells and resulted in marked decryption of TF PCA independent of de novo protein synthesis. This PCA-modulating effect was concomitant with and functionally dependent on the exposure of phosphatidylserine on the outer membrane leaflet. Similar observations were made in analogous ex vivo studies on patient-derived myeloblasts. Incubation of HL60 cells with GM-CSF, a cytokine expressed in the bone marrow microenvironment and used as an adjunct to AML treatment, evoked a cellular response, which included both enhanced TF production and release of VEGF-A and uPA into the culture medium. We conclude that both decryption of pre-formed TF PCA by chemotherapeutic drugs and de novo induction of TF by cytokines such as GM-CSF can regulate the pro-coagulant phenotype of HL60 cells in vitro.

Antineoplastic Agents↗

Heterogeneity of functional responses in differentiated myeloid cell lines reveals EPRO cells as a valid model of murine neutrophil functional activation.

Mature neutrophils display multiple functional responses upon activation that include chemotaxis, adhesion to and transmigration across endothelial cells, phagocytosis, and pathogen destruction via potent microbicidal enzymes and reactive oxygen species. We are using myeloid cell line models to investigate the signaling pathways that govern neutrophil functional activation. To facilitate these studies, we have performed a direct comparison of functional responses of human and murine myeloid cell line models upon neutrophil differentiation. Our results show that EPRO cells, promyelocytes that undergo complete neutrophil maturation, demonstrate a full spectrum of functional responses, including respiratory burst, chemotaxis toward two murine chemokines, and phagocytosis. We also extend previous studies of granulocyte-colony stimulating factor-induced 32Dcl3 cells, showing they demonstrate chemotaxis and phogocytosis but completely lack a respiratory burst as a result of the absent expression of a critical oxidase subunit, gp91(phox). Induced human leukemic NB4 and HL-60 cells display a respiratory burst and phagocytosis but have defective chemotaxis to multiple chemoattractants. We also tested each cell line for the ability to up-regulate cell-surface membrane-activated complex-1 (Mac-1) expression upon activation, a response mediating neutrophil adhesion and a surrogate marker for degranulation. We show that EPRO cells, but not 32Dcl3 or NB4, significantly increase Mac-1 surface expression upon functional activation. Together, these data show that EPRO and MPRO cells demonstrate complete, functional activation upon neutrophil differentiation, suggesting these promyelocytic models accurately reflect the functional capacity of mature murine neutrophils.

Animals↗

Agar cultures of human clonogenic hemopoietic precursor cells for early diagnosis of some myeloproliferative diseases.

Growth characteristics of human hemopoietic cells in erythremia and chronic myeloid leukemia were studied using agar cultures with and without hemopoietic growth factors. Agar cultures, similarly to cultures on other semisolid media (plasma clot, methylcellulose) can be used for early differential diagnosis of polycythemia vera (erythremia) and secondary erythrocytosis: erythremia, but not erythrocytosis, is characterized by spontaneous (erythropoietin-independent) formation of colonies from erythrocyte precursor cells. Spontaneous colony formation from granulocyte-macrophage precursor cells can serve as an important test for early diagnosis of chronic myeloid leukemia. The study of colony formation from granulocyte-macrophage precursors and of the capacity of bone marrow cells to form colonies from hemopoietic stromal precursor cells revealed new characteristics of the studied myeloproliferative diseases. Presumably, spontaneous colony formation from erythrocytic and myeloid precursors should be regarded as a sign of tumor transformation of the studied hemopoietic cells.

Agar↗

Further studies on the biological activities of the CFU-S inhibitory tetrapeptide AcSDKP. I. The precise point of the cell cycle sensitive to AcSDKP. Studies on the effect of AcSDKP on GM-CFC and on the possible involvement of T-lymphocytes in AcSDKP response.

In order to further investigate the mechanisms of spleen colony-forming unit (CFU-S) inhibition by the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), the following related subjects were studied: 1) the effects of AcSDKP on the kinetics of granulocyte and macrophage precursor cells (granulocyte-macrophage colony-forming cells; GM-CFC); 2) the precise point in the cell cycle of CFU-S that is sensitive to AcSDKP; and 3) the role of lymphocytes in the chain of events leading to the inhibition of CFU-S entry into the cell cycle. The effects of AcSDKP on CFU-S and GM-CFC were tested using the spleen colony assay and methylcellulose culture technique, respectively; the cell cycle kinetic status was determined by the tritiated thymidine suicide technique. Nude mice were studied to assess the role of T-lymphocytes in the inhibitory phenomenon. Our results indicate that: 1) there is no inhibitory effect of AcSDKP on GM-CFC in vitro or in vivo; 2) AcSDKP is active at only the G0 or early G1 phases; and 3) AcSDKP activity is not modulated by T cells.

Amino Acid Sequence↗

Changes in the hemopoietic system of mice deficient for tumor necrosis factor or lymphotoxin-alpha.

Hemopoietic and stromal precursor cells were studied in mice deficient for tumor necrosis factor or lymphotoxin-alpha. In normal hemopoiesis the main characteristics of hemopoiesis in knockout mice did not differ from those in wild-type mice. Implantation of bone marrow cells from mice deficient for tumor necrosis factor onto irradiated sublayer of a long-living bone marrow culture led to a notable increase in the number of mature cells and granulocytic-macrophage precursor cells. This can be due to the fact that tumor necrosis factor inhibits proliferation of hemopoietic precursor cells, while in the absence of this factor precursor cells actively proliferate. On the other hand, cell composition and number of colony-forming units of granulocytes-macrophages are significantly decreased in cultures onto which bone marrow cells from lymphotoxin-alpha-deficient mice were implanted. This can be explained by impaired expression of adhesion molecules in these animals. In addition, the number of stromal precursor cells was changed in mice deficient by genes of the tumor necrosis factor cluster.

Animals↗

Lack of effect of a granulocyte proliferation inhibitor or their committed precursor cells.

Using the agar culture technique, we have measured the effect of granulocyte extracts GCE (and of erythrocyte-RCE and lymph node extracts-LNE) on the growth and proliferation of the committed granulocytic precursor cells, CFU-C. In addition we have determined their effects on the proliferation of the developing colony cells and on the ultimate cell production in the colonies. The results show that GCE has no effect on the growth or proliferative activity on the CFU-C. It does, however, reduce both the autoradiographic labelling indices of the developing colony cells and the net colony cellularities, acting as a cell cycle modulator. These are effects specific to the GCE since at the dose levels used, neither RCE nor LNE affected these measurements.

Animals↗