Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

An in vitro liquid suspension culture system was used to determine the role of cytokines in sustaining long-term human megakaryocytopoiesis. Bone marrow cells expressing CD34 but not HLA-DR (CD34+DR-) were used as the inoculum of cells to initiate long-term bone marrow cultures (LTBMC). CD34+DR- cells (5 x 10(3)/mL) initially contained 0.0 +/- 0.0 assayable colony-forming unit-megakaryocytes (CFU-MK), 6.2 +/- 0.4 assayable burst-forming unit-megakaryocytes (BFU-MK), and 0.0 +/- 0.0 megakaryocytes (MK). LTBMCs were recharged every 48 hours with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-3, and/or IL-6, alone or in combination. LTBMCs were demidepopulated weekly or biweekly, the number of cells and MK enumerated, and then assayed for CFU-MK and BFU-MK. LTBMCs receiving no cytokine(s) contained no assayable CFU-MK or BFU-MK and no observable MK. LTBMCs receiving GM-CSF, IL-1 alpha, and/or IL-3 contained assayable CFU-MK and MK but no BFU-MK for 10 weeks of culture. The effects of GM-CSF and IL-3, IL-1 alpha and IL-3, but not GM-CSF and IL-1 alpha were additive with regards to their ability to augment the numbers of assayable CFU-MK during LTBMC. LTBMCs supplemented with IL-6 contained modest numbers of assayable CFU-MK for only 4 weeks; this effect was not additive to that of GM-CSF, IL-1 alpha, or IL-3. The addition of GM-CSF, IL-1 alpha, and IL-3 alone or in combination each led to the appearance of significant numbers of MKs during LTBMC. By contrast, IL-6 supplemented cultures contained relatively few MK. These studies suggest that CD34+DR- cells are capable of initiating long-term megakaryocytopoiesis in vitro and that a hierarchy of cytokines exists capable of sustaining this process.
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PMID:Role of cytokines in sustaining long-term human megakaryocytopoiesis in vitro. 137 Mar 83

Human interleukin 3 (IL-3) is a multipotential cytokine that supports the growth of early hematopoietic progenitors and promotes their response to other, later-acting cytokines. We found that IL-3 was able to induce the expression of interleukin 2 (IL-2) receptor (IL-2R) (CD25) on a subset of early myeloid cells in normal human bone marrow that had been first depleted of mature hematopoietic cells and E-rosette-positive T cells by treatment with soybean lectin and sheep erythrocytes (SBA-E-BM). Immunofluorescence analysis revealed that the CD25+ cells were contained almost entirely within the lymphoblastoid gate of the IL-3-cultured marrow. CD25 was undetectable on freshly isolated marrow and less than 10% CD25+ cells could be detected following liquid culture at 37 degrees C in the presence of 10% human serum, 10% fetal calf serum, or under serum-free conditions. Addition of IL-3 (100 U/ml) significantly increased the expression of CD25 to 37%, 31%, and 24%, respectively. CD25 could also be induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), but no IL-2R was detectable following exposure to granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), interleukin 1 (IL-1), interleukin 4 (IL-4), or IL-2. Expression of CD25 was dependent on the dose of IL-3 or GM-CSF added and was maximal within 24 h of exposure. Two-color immunofluorescence analysis demonstrated that CD25 was not expressed by cells of lymphoid lineage or by mature monocytes, but rather was present on cells that coexpressed CD13, CD33, CD34, MY8, and HLA-DR, and that lacked CD14 or CD11b, thus placing the CD25+ cells at or near the myeloblast stage of differentiation. An identical phenotype was found for CD25+ cells induced by GM-CSF. Cycloheximide completely inhibited the IL-3-induced expression of CD25, indicating the necessity for protein synthesis, and although most of the CD25+ cells were in G0/G1 phase, 25% of the cells were in S or G2M phase, indicating that receptor expression was not cell-cycle dependent. The p75 chain of IL-2R was not detected on the CD25+ cells. IL-3 was also found to directly induce CD25 in greater than 46% of SBA-E-BM enriched for CD34+ cells by panning. Consistent with the expression of only p55 IL-2R, the functional activity of IL-2 on enriched CD34+ cells exposed to IL-3 could not be demonstrated in either granulocyte-macrophage colony-forming unit (CFU-GM) assays or proliferation assays.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recombinant interleukin 3 induces interleukin 2 receptor expression on early myeloid cells in normal human bone marrow. 137 65

The in vitro growth of early (megakaryocyte burst-forming units, BFU-meg) and late (megakaryocyte colony-forming units, CFU-meg) megakaryocyte (meg) progenitors has been evaluated in normal adult human peripheral blood (PB). All the experiments were carried out using CD34+ cells, which were assayed in a serum-free fibrinclot assay. PB BFU-meg were morphologically characterized as plurifocal aggregates containing greater than 50 cells/colony, distinct from unifocal CFU-meg, in a limiting dilution assay. At variance with PB CFU-meg, PB BFU-meg were unaffected by the complement-mediated cytotoxicity with anti-HLA-DR. The optimal source of colony-stimulating activity for PB BFU-meg growth was recombinant human interleukin 3 (rhIL-3; 100 U/ml), which supported a significantly higher number of BFU-meg in comparison with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 200 U/ml, p = 0.043). Combinations of rhIL-3 (100 U/ml) plus rhGM-CSF (200 U/ml), rhIL-3 plus recombinant human interleukin 6 (rhIL-6; 100 U plus 100 U/ml) or rhIL-3 plus rhGM-CSF plus rhIL-6 (100 U plus 200 U/ml plus 100 U/ml) failed to further increase the number of PB BFU-meg with respect to rhIL-3 (100 U/ml) alone. Both PB BFU-meg and CFU-meg were markedly inhibited, in a dose-dependent fashion, by increasing doses of human purified transforming growth factor-beta 1 (TGF-beta 1) (from 0.001 to 10 ng/ml). Finally, the CFU-meg/BFU-meg ratio in PB (0.52) was significantly different from that of normal bone marrow (2.3), clearly indicating that adult human peripheral blood predominantly carries primitive megakaryocytic progenitors.
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PMID:Prevalence of the primitive megakaryocyte progenitors (BFU-meg) in adult human peripheral blood. 137 7

In this study we have made a detailed analysis of growth factor (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF], and macrophage colony-stimulating factor [M-CSF])-induced proliferation and differentiation of highly purified CD34+ committed human myeloid progenitor cells in suspension cultures. The results were compared with colony formation in semisolid medium. Proliferation in suspension cultures was determined by means of incorporation of [3H]thymidine, differentiation by flow cytometric immunophenotyping using a panel of monoclonal antibodies against monomyeloid antigens, and by morphology. A good correlation was found between the number of granulocyte-macrophage colony-forming units (CFU-GM) in semisolid medium and [3H]thymidine incorporation in suspension (r = 0.82), both assessed at day 11. Moreover, the frequency of proliferating cells as determined in suspension cultures by limiting dilution analysis was similar to the frequencies of CFU-GM as measured in semisolid medium. Studies on GM-CSF- and G-CSF-induced cell-growth kinetics revealed distinct proliferation patterns. Immunophenotypically the subsequent induction of the mature granulocytic antigens CD15 and CD67 was observed to be accompanied by a gradual loss of the HLA-DR antigen, whereas little monocytic differentiation was observed. M-CSF, although inducing no colony formation of CD34+ cells and minimal proliferation in suspension, induced monocytic differentiation, demonstrated by the expression of HLA-DR, CD14, and CD36 in the absence of CD15 and CD67. The observed immunophenotypical profiles were confirmed by the results of cytological characterization. Thus, the combined measurement of growth factor-induced proliferation and differentiation of progenitor cells in suspension cultures can be a useful alternative for the CFU-GM assay. Moreover, because small numbers of cells are required, it allows for detailed studies on cell-growth kinetics and developmental stages within the granulocytic and monocytic lineages.
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PMID:Combined measurement of growth and differentiation in suspension cultures of purified human CD34-positive cells enables a detailed analysis of myelopoiesis. 138 96

The myeloid-monocytic cells ML-1, HL-60, THP-1, and U-937 were chronically infected (for > 2 years) with the lymphotropic human immunodeficiency virus type 1 (HIV-1) strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1/HIV-1 and HL-60/HIV-1 cells showed a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-1/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers revealed a differential expression of CD4, CD8, CD11c, CD14, CD15, CD20, HLA-DR, and HLA-DQ in non- or chronically infected cells. In chronically infected cells, the steady-state levels for tumor necrosis factor-alpha, interleukin (IL)-1 beta, and granulocyte-macrophage colony-stimulating factor mRNA remained unchanged whereas the one for IL-6 dropped.
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PMID:Characterization of human immunodeficiency virus-1-infected cells of myeloid-monocytic lineage (ML-1, HL-60, THP-1, U-937). 145 15

We investigated the in vitro hematopoietic stimulatory activity of leukemia inhibitory factor/human interleukin for DA cells (LIF/HILDA) on bone marrow progenitor populations in 17 normal individuals. In serum-free cultures LIF/HILDA did not induce colony growth. In serum containing media, LIF/HILDA stimulated the growth of colony forming unit (CFU)-MIX and CFU-EO in a dose-dependent fashion and resulted in an increased CFU-MIX and burst forming unit-erythrocytes (BFU-E) colony size. Similar stimulatory effects were seen on a highly purified hematopoietic progenitor population obtained after immunomagnetic depletion of mature myeloid precursors and lymphoid cells. Addition of LIF/HILDA to cultures containing maximally stimulatory concentrations of recombinant human interleukin-3 (rhuIL3), rhuIL3 + rhuIL6, or rhu granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) in serum containing media significantly increased the number of CFU-MIX and eosinophil colonies and increased size and cluster number of CFU-MIX and BFU-E. Depletion of accessory T lymphocytes or monocytes from bone marrow progenitors did not alter the response of hematopoietic precursors to LIF/HILDA. A similar increased colony growth was seen when LIF/HILDA was added to cultures of positively selected CD34/HLA-DR+ or CD34+/HLA-DR- bone marrow hematopoietic progenitor cells stimulated with maximally stimulatory concentrations of rhuIL3 + rhuIL6. LIF/HILDA is a novel cytokine capable of stimulating growth and proliferation of multi-lineage, erythroid, and eosinophil colonies in the presence of serum. LIF/HILDA exerts its activity by direct interaction with highly purified immature bone marrow progenitor cells, has an additive effect when used with other cytokines known to stimulate primitive hematopoietic precursors, and does not require accessory cells.
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PMID:Leukemia inhibitory factor/human interleukin for DA cells: a growth factor that stimulates the in vitro development of multipotential human hematopoietic progenitors. 170 32

Our experiments were directed towards the detection of the influence of interleukin-1 (IL-1); interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the generation of granulocyte-macrophage progenitor cells. We also set out to examine whether this process is connected with changes within the early precursor cell compartment. Bone marrow suspension cultures (12 days) supplemented with these cytokines were tested for the presence of GM colony-forming cells (GM-CFC) in a colony-forming unit assay. The percentage of CD34+ and HLA-DR+ as well as the number of blasts and promyelocytes were estimated cytofluorometrically and morphologically. The proliferative effect of GM-CSF was associated with a net increase of GM-CFC and HLA-DR+ myeloid cells and a decrease in the percentage of CD34+ early precursor cells. IL-3 acted similarly and also caused an absolute decrease of CD34+ cells in the cultures. IL-1 did not stimulate the generation of blasts or GM-CFC but elevated the number of CD34- as well as HLA-DR-expressing cells in the cultures. These results imply that GM-CSF supported the maintenance of hematopoiesis in vitro. The transition from early precursor cells to committed myeloid progenitor cells (GM-CFC) and more mature precursor cells (G-CFC, M-CFC) may be supported by GM-CSF without affecting the self-renewing capacity of CD34+ early precursors. In contrast, the blast-generating and proliferation-inducing action of IL-3 is associated with a drop in the total number of CD34+ stem cells. An efficient renewal of this population obviously depends on the presence of IL-1.
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PMID:Comparative analysis of the influences of IL-1, IL-3 and GM-CSF on the commitment of granulocyte-macrophage progenitors in vitro. 172 Mar 32

The development and function of eosinophils are regulated by a number of cytokines. Three cytokines have major effects on eosinophilopoiesis. Both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 stimulate the development of eosinophils as well as other leukocytes. Interleukin-5 promotes eosinophil development and terminal differentiation. These three cytokines also effect the functions of mature eosinophils and can prolong their longevity in in vitro culture, enhance their capacity for release of leukotriene C4 (LTC4), augment their capacity for helminthotoxicity and degranulation, and render them less dense ("hypodense") than normal, unactivated eosinophils. GM-CSF can also induce the expression of HLA-DR on mature eosinophils, which can enable eosinophils to serve as antigen-presenting cells in stimulating T-cell responses. A T-cell-derived cytokine, lymphocyte chemoattractant factor (LCF), which stimulates the migration and function of CD4+ lymphocytes and eosinophils, also utilizes CD4 expressed on human eosinophils as its receptor. LCF stimulates eosinophil migration but not degranulation, leukotriene C4 release, or respiratory burst activity. Interleukin-2 is also a potent chemoattractant for eosinophils. Thus, cytokines are involved in both increased production of eosinophils as well as regulation of the functions of mature eosinophils. These functions of mature eosinophils include effector functions and collaborative interactions with lymphocytes and other tissue cellular elements.
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PMID:Cytokine regulation of eosinophil function. 172 88

We investigated the effects of several cytokines on HLA-DR expression in cultured fibroblasts derived from retroocular connective tissue and pretibial and abdominal skin of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD), as well as from normal individuals. We hypothesized that differences in response to cytokines between fibroblasts from various anatomical areas might play a role in the site-selective involvement of the extrathyroidal manifestations of Graves' disease. HLA-DR expression in fibroblasts was quantitated by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Direct immunofluorescence of cell monolayers was also performed. We hypothesize that unique characteristics of these fibroblasts may play a role in GO and PTD. Cultured retroocular, pretibial, and abdominal fibroblasts from patients with Graves' disease as well as from normal individuals did not express HLA-DR spontaneously. Treatment in vitro with interferon-gamma (IFN gamma; 100 U/mL) for 5 days induced HLA-DR by 50- to 80-fold (P less than 0.0001) in fibroblasts from all sites and subjects studied. However, IFN gamma-induced HLA-DR expression was significantly greater in retroocular (P less than 0.005) and pretibial (P less than 0.0005) fibroblasts from patients with GO and PTD than in fibroblasts obtained from the same anatomical sites of normal individuals. Further, retroocular and pretibial fibroblasts from patients with GO and PTD responded to IFN gamma more vigorously than did abdominal fibroblasts from these same patients (P less than 0.0001). IFN gamma-induced HLA-DR expression was enhanced by concomitant treatment with tumor necrosis factor-alpha (100 U/mL). In contrast, treatment of retroocular fibroblasts with transforming growth factor-beta (10 ng/mL), epidermal growth factor (1 ng/mL), or interleukin-6 (IL-6; 100 U/mL) significantly attenuated IFN gamma-induced HLA-DR reactivity by 40-59% (P less than 0.05). Incubation of retroocular fibroblasts with tumor necrosis factor-alpha, IL-1 alpha (10 U/mL), IL-2 (10 U/mL), IL-6, granulocyte-macrophage colony-stimulating factor (100 U/mL), epidermal growth factor, and transforming growth factor-beta alone did not affect HLA-DR expression. These results indicate that several cytokines can influence HLA-DR expression in cultured fibroblasts. The enhanced induction of HLA-DR by IFN gamma in retroocular and pretibial fibroblasts compared with that in abdominal fibroblasts may partially explain the selective involvement of the retroocular connective tissue and pretibial skin in fully expressed Graves disease.
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PMID:Increased induction of HLA-DR by interferon-gamma in cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial dermopathy. 190 94

Various concentrations of 1,25-dihydroxyvitamin D3 (vit D3; 10(-9)-10(-7) M) and recombinant human tumor necrosis factor alpha (rTNF-alpha; 60-960 U/ml) were used to induce growth inhibition and differentiation of the human promyelocytic leukemia cell line HL-60 based on growth kinetics, colony formation, morphological analysis, nonspecific esterase (NSE) activity, surface antigen expression, and cytokine release. Both vit D3 (10(-8)-10(-7) M) and rTNF-alpha (60-960 U/ml) were antiproliferative against the HL-60 cells, and a cooperative effect was noted when the two inducers were used in combination. After 5 days of incubation, vit D3 induced the HL-60 cells to differentiate into monocytes/macrophages, resulting in the formation of 3.0% +/- 0.4%, 18% +/- 2.0%, and 43% +/- 3.8% of morphologically mature cells at 10(-9), 10(-8), and 10(-7) M, respectively. The induced cells were NSE positive and expressed monocyte-associated antigens (EBM11, CD11b, and HLA-DR). Conversely, rTNF-alpha (60-960 U/ml) was unable to trigger the HL-60 cells to differentiate. However, rTNF-alpha could apparently increase the proportion of the morphologically mature and NSE-/antigen-positive cells when used in combination with vit D3 (10(-9)-10(-8) M). Following differentiation induction, HL-60 cells from vit D3-treated HL-60 cultures acquired the ability to secrete certain monokines, including interleukin 1 beta (IL-1 beta), prostaglandin E2 (PGE2), and granulocyte-macrophage colony-stimulating factor (GM-CSF), and adding rTNF-alpha in addition to vit D3 invariably increased the production of IL-1 beta and PGE2.
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PMID:Growth inhibition and differentiation in HL-60 leukemia cells induced by 1,25-dihydroxyvitamin D3 and tumor necrosis factor alpha. 191 3


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