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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of mitogens and/or recombinant B-cell growth factors (M/GFs) on the in vitro growth of hairy cells was examined. Tumor cells were isolated from the spleens of four patients with hairy cell leukemia (HCL) by Ficoll-Hypaque sedimentation and E-rosetting. Enrichment for tumor cells was confirmed with intracytoplasmic immunoglobulin (Ig) staining, tartrate resistant acid phosphatase (TRAP) staining, and staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, and monocytoid antigens (Ags) in indirect immunofluorescence assays. Tumor cells were B1(CD20)+ B2(CD21)- B4(CD19)+ IL-2R(CD25)+ PCA-1 +/- TRAP+. HCLs neither synthesized DNA nor secreted Ig in response to culture with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, or IL-6. However, a proliferative response (stimulation index greater than or equal to 3.0) without Ig secretion was triggered in HCLs by mitogens or combinations of GFs. Specifically, DNA synthesis was induced at 3 days in three of four HCL samples cultured with Staphylococcus aureus Cowan A (SAC) or the combination of phorbol ester (TPA) and the calcium ionophore A 23187 (Ca2+); DNA synthesis was triggered later (day 7) by tumor necrosis factor (TNF) or by IL-4 and IL-5. In contrast, the fourth patient, a nonresponder to SAC or TPA/Ca2+, demonstrated increased DNA synthesis at day 3 when cocultured with IL-4 and IL-5. Both autoradiography and staining with antibromodeoxyuridine (BrdU) MoAb conjugated to fluorescein confirmed DNA synthesis by only a minority (5% to 23%) of tumor cells within each patient. Dual staining confirmed that responsive cells were both BrdU+ and TRAP+. DNA synthesis induced by TPA/Ca2+ was blocked specifically by anti-IL-6 Ab; in contrast, the HCL proliferative response to SAC, TNF, or IL-4 and IL-5 was not inhibited by anti-IL-6 Ab. alpha-Interferon inhibited the response to TPA/Ca2+, TNF, or IL-4 and IL-5 without any effect on response to SAC. Finally, peroxidase-antiperoxidase staining demonstrated that HCLs are induced by TPA/Ca2+, but not by SAC, to produce intracytoplasmic IL-6. These data demonstrate IL-4, IL-5, and IL-6 mediated DNA synthesis by HCLs in vitro and suggest a possible in vivo role for these growth factors in the pathophysiology of HCL.
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PMID:Response patterns of hairy cell leukemia to B-cell mitogens and growth factors. 224 29

We have examined the biologic and physical properties of a human T-lymphocyte granulocyte-macrophage colony-stimulating factor (CSF). The source of the factor is a T-lymphoblast cell line (Mo) that was derived from a patient with a T-cell variant of hairy-cell leukemia. The Mo line constitutively produces a number of lymphokines that are normally produced by mitogen-stimulated T lymphocytes. Medium conditioned by Mo cells grown in the absence of serum is especially rich in CSF activity, and using this source we have purified the CSF to a specific activity of about 3.5 x 10(6) colonies per 10(5) Ficoll-Hypaque-separated human bone marrow cells plated per mg protein. The Mo CSF stimulates the formation of both granulocyte and macrophage colonies in vitro (in about equal numbers) and it has a relatively steep dose-response curve. Both the crude and purified preparations stimulated the formation of eosinophil as well as neutrophil colonies; it is unclear whether this is due to the presence of multiple factors with similar physical properties or a single factor with multiple activities. The CSF has little stimulating activity for mouse bone marrow progenitors. Physically, the Mo CSF is an acidic glycoprotein of molecular weight about 34,000. It binds to concanavalin A-Sepharose, is unusually resistant to denaturing agents and heat treatment, and is not inactivated in the presence of sulfhydryl reagents. The Mo CSF is distinct from factors stimulating erythroid colony formation and inhibiting neutrophil migration that are also produced by Mo cells. It differs in several physical and biologic properties from other human CSFs that have been characterized.
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PMID:Purification and characterization of a human T-lymphocyte-derived granulocyte-macrophage colony-stimulating factor. 696 9

Granulocyte-macrophage colony-stimulating factor (GM-CSF) production by the peripheral blood (PB) cells of hairy cell leukemia (HCL) patients whose PB contained only 2 to 10% hairy cells was studied in an in vitro bone marrow culture system. In addition, the possible inhibitory effect on the growth of normal granulocyte-macrophage colony-forming cells (GM-CFC) by the patients' mononuclear cells or serum was assayed. GM-CSF production by PB cells of HCL patients was 82 +/- 18% (mean +/- sd) lower than its production by normal PB cells. No significant inhibition of normal GM-CFC growth was observed in the presence of patients' PB mononuclear cells or their serum. These findings suggest that in HCL patients the monocyte-macrophage system is defective in its capacity to produce GM-CSF. This defect may play a role in the impaired granulocyte production known to occur in HCL.
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PMID:Hairy cell leukemia: defective production of granulocyte-macrophage colony-stimulating factor by peripheral blood cells. 698 26

Granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors (GMR) are expressed on myeloid cells throughout their maturational sequence. During myelopoiesis, GM-CSF induces the proliferation of precursors and has multiple effects on more mature cells; such effects include induction of maturation and priming for subsequent stimulation. GMR is expressed on a range of other cell types including acute leukemic blasts of myeloid and lymphoid lineage, but has been little studied on more mature lymphoid cells. Using sensitive triple-layer immunophenotypic techniques, we show here that both the alpha and beta c chains of the GMR are expressed on hairy cells (HCs) and myelomatous plasma cells (PCs), but not on chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) lymphocytes. The receptor was demonstrable on normal PCs in tonsil, but not on either activated or resting tonsillar B cells or on circulating normal B lymphocytes. The expression of the receptor is therefore stage specific, rather than a feature of activation. Perhaps, surprisingly, in view of its effects on myeloid cells, GM-CSF did not stimulate the proliferation or differentiation of HCs and did not protect them from apoptosis. However, the cytokine had a profound effect on the interaction of the HC with its environment. Thus, the cytokine caused a major cytoskeletal reorganization resulting in the inhibition of motility and loss of adhesion to cellular and matrix ligands. These studies indicate the importance of GM-CSF outside myelopoiesis and demonstrate a previously unrecognized stage specific role for the cytokine in B-cell biology. Taken together with our previous report that M-CSF enhances B-cell motility, the present findings indicate that myeloid growth factors act in concert to facilitate the controlled migration of certain B cells into and within tissues.
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PMID:Granulocyte-macrophage colony-stimulating factor receptor: stage-specific expression and function on late B cells. 869 95

The course of hairy cell leukemia (HCL) is characterized by progressive pancytopenia. The pathogenesis of this phenomenon is still not fully understood. To study if the decrease in hematopoiesis in HCL is accompanied by abnormal concentrations of growth factors, we investigated the production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 3 (IL-3), interleukin 6 (IL-6), and tumor necrosis factor alpha by peripheral blood mononuclear cells (PBMCs) of eight patients with HCL. The results point to a severe deficiency of production of all cytokines tested as compared to healthy donors. However, enrichment of autologous monocytes by counterflow centrifugation resulted in a marked increase of the levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-6, and tumor necrosis factor alpha. The most pronounced effects were seen with IL-6. Reverse transcription-PCR analysis indicated that pokeweed mitogen, IFN-alpha, and poly(I:C) are capable of inducing the expression of IL-6-specific mRNA in HCL cells. These findings are substantiated on the protein level by immunofluorescence analysis. Incubation of PBMCs with IFN-alpha resulted in a significant increase of intracellular IL-6 in HCL but not in healthy donors. This increase was also seen in hairy cells positive for CD19 and CDllc. Furthermore, IFN-alpha induced the secretion of IL-6 from PBMCs of HCL patients but not healthy donors. In conclusion, our studies with PBMCs from patients with HCL revealed an inadequate supply of hematopoietic growth factors that might, in part, be due to the monocytopenia characteristic for this disease. The findings also indicate that IFN-alpha is capable of inducing the production of IL-6 in the patients' PBMCs as well as in their hairy cells. These data from our in vitro studies support the clinical observation that treatment with IFN-alpha leads to reconstitution of hematopoiesis.
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PMID:Inadequate production of hematopoietic growth factors in hairy cell leukemia: up-regulation of interleukin 6 by recombinant IFN-alpha in vitro. 884 Sep 84

We describe a case of successfully treated multifocal pulmonary Rhizomucor pusillus, a condition which has previously been universally fatal. A 77 year-old man had a background of chronic neutropenia due to hairy-cell leukemia, splenectomy, corticosteroid therapy and an obstructing left ureteric transitional-cell carcinoma. He was successfully treated with 3 months of high-dose liposomal amphotericin B and 7 months of granulocyte-macrophage colony-stimulating factor. Treatment was complicated by mild reversible deterioration of renal function. There was a near complete radiological response to the therapy at 6 months and the patient remains well 20 months following diagnosis of R. pusillus and 13 months following cessation of treatment.
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PMID:Cure of pulmonary Rhizomucor pusillus infection in a patient with hairy-cell leukemia: role of liposomal amphotericin B and GM-CSF. 1191 24

The Notch/Notch ligand system controls diverse cellular processes. The proteolytic cleavage generates transmembrane and soluble forms of Notch ligands. We examined the effect of a soluble Notch ligand, human Jagged-1, on human cord blood (CB) CD34+ cells, under serum-deprived conditions, using soluble human Jagged-1-immunoglobulin G1 chimera protein (hJagged-1). Soluble hJagged-1 inhibited myeloid colony formation but not erythroid-mix or erythroid colony formation, in the presence of stem cell factor (SCF), interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, thrombopoietin, and erythropoietin. Cytological analysis revealed that the decrease in myeloid colonies resulted mainly from the inhibition of macrophage colony formation. Furthermore, soluble hJagged-1 led to the inhibition of macrophage colony formation supported by M-CSF plus SCF and GM-CSF plus SCF. Delayed-addition experiments and the analysis of colony sizes demonstrated that soluble hJagged-l inhibited the growth of macrophage progenitors by acting in the early stage of macrophage development. The direct action of hJagged-1 was confirmed by the enhanced expression of the HES-1 (hairy enhancer of the split-1) gene. These results suggest that soluble hJagged-1 may regulate human hematopoiesis in the monocyte/macrophage lineage.
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PMID:The soluble Notch ligand, Jagged-1, inhibits proliferation of CD34+ macrophage progenitors. 1199 54