UNIPROT:P04141 - FACTA Search

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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 human monoblast cell line, U937, was employed to elucidate early events associated with differentiation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) and 1,25-dihydroxy-Vitamin D3 (VD3). Exposure of cells to a combination of GM-CSF and VD3 resulted in an up-regulation of c-fos mRNA within 1 h and a marked down-regulation of c-myc mRNA by 24 h and this was associated with a shift of cell population from the S phase to the G0 + G1 phase of the cell cycle by 18%. This was followed by a marked enhancement of monocyte-associated cell surface antigens [OKM1 (CD11b), LeuM3 (CD14), M77.7], as determined by monoclonal antibodies and flow cytometry. Functional characteristics such as nitroblue-tetrazolium reduction, alpha-naphthyl butyrate esterase activity, and phagocytic capability occurred. Cells treated with GM-CSF or VD3 alone showed only minor changes. These results demonstrate a potent synergistic effect of GM-CSF and VD3 on induction of U937 differentiation. This differentiation was partially blocked by H7, a protein kinase C (PKC) inhibitor. Changes in c-myc and c-fos mRNA expressions and a shift in cell cycle were shown to be early events in this process.
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PMID:Mechanisms of differentiation of U937 leukemic cells induced by GM-CSF and 1,25(OH)2 vitamin D3. 186 27

We studied the influence of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF), human recombinant interferon-gamma (hrIFN-gamma) and splenopentin pentapeptide (Sp-5), either alone or in combination, on the proliferation and differentiation of human bone marrow cells in modified Dexter's cultures. After 10, 14 and 21 days cells were analyzed by classical staining according to Pappenheim and by cytofluorometry with a set of different monoclonal antibodies. IFN-gamma inhibited the proliferation of progenitor cells and provided signals promoting monocytic differentiation, whereas GM-CSF induced the proliferation of blastoid elements which expressed HLA-DR and M2 (VIM-2 monoclonal antibody), but progressively lost surface CD34. Furthermore, an increase of CD15+ cells was also observed. When GM-CSF was tested in combination with IFN-gamma, it abolished the inhibitory effect of IFN-gamma and both cytokines synergized to promote the expression of CD11c, CD14 and M2 surface antigens. Sp-5 alone had only a marginal activity, but it potentiated the effects of GM-CSF. These findings suggest that GM-CSF may induce the transition from stem cells to committed myeloid progenitors. In contrast to IFN-gamma, Sp-5 can serve as an additional proliferative signal with negligible effects on cell maturation.
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PMID:Cytofluorometric and cytomorphologic analysis of human bone marrow cells derived from stromal cultures stimulated by granulocyte-macrophage colony-stimulating factor, interferon-gamma and splenopentin pentapeptide. 211 95

A new human myeloid cell line has been established recently from the bone marrow cells of a patient with chronic myelogenous leukemia in blast crisis. The active proliferation and survival of the cells in RPMI 1640 medium containing fetal calf serum are clearly dependent on the presence of either natural or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Despite permanent culturing in rhGM-CSF (100 U/mL), the cells do not differentiate and bear the myelomonocytic surface markers CD34, CD13, CD36, as well as HLA-DR, but not CD3, CD7, CD10, CD11b, CD14, CD20, or CD42b. The predominant karyotype, apart from tetraploidy in several cells, is 45, XX, -9, -17, -19, -22, 7p-, 9q+ (der t[9;22]), der (13q), with three additional marker chromosomes, from which one was observed in the patient's leukemic cells. On BglII-digested DNA, Southern blot analysis with bcr 5' as the probe detected two additional hybridizing restriction fragments of 8.6 and 11.0 kilobase pairs.
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PMID:Establishment and characterization of a granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line. 219 61

Using an in vitro expansion and differentiation system for human CD34+ cord blood (CB) progenitor cells, we analyzed the induction and expression kinetics of the granulomonocyte associated lysosomal proteins myeloperoxidase (MPO), lysozyme (LZ), lactoferrin (LF), and macrosialin (CD68). Freshly isolated CD34+ CB cells were negative for LZ and LF, and only small proportions expressed MPO (4% +/- 2%) or CD68 (3% +/- 1%). Culturing of CD34+ cells for 14 days with interleukin (IL)-1, IL-3, IL-6, stem cell factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF resulted in on average a 1,750-fold amplification of cell number, of which 83% +/- 7% were MPO+. Without addition of GM-CSF and G-CSF, lower increases in total cell numbers (mean, 211-fold) and lower proportions of MPO+ cells (54% +/- 11%) were observed. The proportion of MPO+ cells slightly exceeded but clearly correlated with the proportion of cells positive for the granulomonocyte associated surface molecules CD11b (Mac-1), CD15 (LeX), CD64 (Fc gamma RI) CD66, or CD89 (Fc alpha R). At day 14 MPO+ and LZ+ cells were virtually identical. However, at earlier time points during culture (days 4 and 7), single MPO+ or LZ+ cell populations were also observed, which only later acquired LZ and MPO, respectively. Maturation of cells into the neutrophilic pathway was indicated by the acquisition of MPO, followed by LZ. In contrast, maturation of cells into the monocytic pathway was indicated by the acquisition of LZ followed by MPO and CD14. CD68 was found to be expressed at day 4 by the majority of cells and was not restricted to the granulomonocytic cells, as cells with megakariocytic (CD41+) or erythroid (CD71hi) features were CD68+. LF expression was observed only in GM- plus G-CSF-supplemented cultures, in which only 26% +/- 5% of cells expressed LF by day 14.
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PMID:Granulomonocyte-associated lysosomal protein expression during in vitro expansion and differentiation of CD34+ hematopoietic progenitor cells. 749 68

The effect of cytokines on the proliferation and differentiation of leukemia cells from 5 patients with acute promyelocytic leukemia (APL) was examined. Interleukin-1 beta (IL-1), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) augmented uptake of 3H-thymidine into the DNA of APL cells in a dose-dependent manner in all cases. This stimulatory effect was pronounced in some, but not all, cells treated with all-trans retinoic acid (ATRA). However, nitroblue tetrazolium-reducing activity was induced in a concentration-dependent manner by ATRA in all cases. The cytokines greatly enhanced NBT reduction of APL cells treated with ATRA, and a mixture of cytokines was more effective than a single cytokine. Although GM-CSF, IL-3 and IL-1 significantly modulated the ATRA-induced morphological changes, they did not induce CD14 expression, a typical marker of monocytic differentiation. In the presence of ATRA, GM-CSF potentiated production and secretion of tumor necrosis factor-alpha (TNF) in response to lipopolysaccharide, as well as interferon-gamma which is a potent inducer of monocytic differentiation in APL cells. On the other hand, production of TNF in ATRA-treated cells was not affected by G-CSF which significantly enhanced granulocytic differentiation. The effect of cytokines on APL cell differentiation should be considered in ATRA treatment for APL patients. Potentiation of cytokine production in APL cells associated with myelomonocytic differentiation is noteworthy in the pathogenesis of "retinoic acid syndrome".
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PMID:Effect of cytokines on the proliferation and differentiation of acute promyelocytic leukemia cells: possible relationship to the development of "retinoic acid syndrome". 752 Nov 52

To investigate the regulatory effects of the prototypic Th2 lymphocyte products and potential immunotherapeutic agents interleukin-4 (IL-4) and IL-10 on macrophages differentiated in vitro under different cytokine-defined environments, blood monocytes were incubated for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor or IL-4. The effect of monocyte culture in the presence or absence of serum was also investigated. Functional responses by 7-day-cultured cells to IL-4, quantified as decreased CD14 expression and suppression of lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta production, and as a positive response, increased CD23 expression, were compared directly with the responses by monocytes from which they were derived. In response to IL-10, decreases in LPS-induced TNF-alpha and IL-1 beta production and reduction in the expression of major histocompatibility complex (MHC) class II antigens were examined. Seven-day cultured monocytes/macrophages showed (1) diminished TNF-alpha production in response to IL-10 but not IL-4 (2), diminished IL-1 beta production in response to both IL-4 and IL-10, and compared with fresh monocytes (3), diminished CD14 expression in response to IL-4, and (4) a lesser increase in CD23 expression in response to IL-4. This was the case regardless of the cytokine in the presence of which the cells had been cultured for 7 days. Monocytes cultured for 7 days in GM-CSF expressed increased levels of MHC class II and LPS-induced TNF-alpha and responded inefficiently to IL-10 for decreased MHC class II. The responses by monocytes cultured for 7 days with GM-CSF resemble the published properties of synovial fluid macrophages from patients with chronic inflammatory arthritis. The study highlights the complexity of monocyte/macrophage responses to the immunoregulatory cytokines IL-4 and IL-10 and concludes that responses to IL-4 and IL-10 by blood monocytes may not be representative of responses by their differentiated or activated counterparts.
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PMID:Monocytes cultured in cytokine-defined environments differ from freshly isolated monocytes in their responses to IL-4 and IL-10. 754 Jun 42

Rheumatoid synovitis is characterized by an infiltration of mononuclear cells and by the proliferation of synoviocytes. Monocytes and synoviocytes are major producers of cytokines, growth factors, and enzymes that contribute to the rheumatoid arthritis (RA) process. Since they are in close contact in vivo, we engaged in an in vitro study of the functional consequences of their interactions. Coculture of unstimulated elutriated normal blood monocytes over RA synoviocytes resulted in a synergistic increase of the production of IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), and IL-8, when compared with their respective production in culture alone. In contrast, cytokines such as IL-10, IL-1 beta, IL-1 alpha, and TNF-alpha could not be detected. The IL-6 production in coculture was further increased by the addition of IL-1 beta, GM-CSF, IFN-gamma, or TNF-alpha, but was inhibited by the addition of IL-10, IL-4, IL-13, or IL-1Ra, an effect reverted by the addition of IL-1 beta. Moreover, an inhibition was also observed with anti-CD14 mAb and newly raised mAbs directed against RA synoviocytes. Under reducing conditions, the mAb SY12 precipitated a 150-kDa surface membrane protein, identified as amino-peptidase N (CD13/AP-N). Collectively, these results indicate that 1) monocytes and synoviocytes interact with each other to produce proinflammatory cytokines, 2) pro- and antiinflammatory cytokines have opposite effects on IL-6 production, and 3) molecules such as IL-1, CD14, and CD13 are involved.
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PMID:Contribution of IL-1, CD14, and CD13 in the increased IL-6 production induced by in vitro monocyte-synoviocyte interactions. 756 Oct 64

We investigated, via multicolor flow cytometry, the in vivo effects of colony-stimulating factors (CSFs) on cell size, frequencies, and expression of surface antigens on peripheral blood monocytes from melanoma patients treated concurrently with CSFs and tumor-specific monoclonal antibody (mAb) R24. Recombinant human macrophage colony-stimulating factor (rhM-CSF) increased cell size, relative percentages of monocytes, percentages of CD14+, HLA-DQ+, CD11b+, and CD16+ monocytes, and cell-surface expressions of HLA-DR and CD11b; rhM-CSF also up-regulated cell-surface expression of CD14 on CD14brightCD16- monocytes. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) increased cell size, percentages of CD14+, HLA-DQ+, and CD11b+ monocytes, and cell-surface expressions of HLA-DR, HLA-DQ, CD11b, and CD58. Relative percentages of monocytes and CD16+ cells and cell-surface expression of CD14 on CD14brightCD16- monocytes decreased. In addition, monocytes derived from patients treated with rhM-CSF showed functional activity when assayed in vitro for antibody-dependent cellular cytotoxicity (ADCC). During treatment and coincident with increased CD16 expression, monocytes derived from rhM-CSF patients had enhanced levels of cytotoxicity towards melanoma target cells compared to healthy controls and to patients treated with rhGM-CSF.
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PMID:Alterations in phenotype and cell-surface antigen expression levels of human monocytes: differential response to in vivo administration of rhM-CSF or rhGM-CSF. 758 40

Interleukin-13 (IL-13) is a pleiotropic cytokine that inhibits the production of inflammatory cytokines of monocytes. We investigated the effects of IL-13 on the clonal growth of human hematopoietic progenitors. IL-13 alone did not support any colony formation. IL-13 markedly suppressed macrophage colonies that were formed in the presence of IL-3 and erythropoietin, granulocyte-macrophage colony-stimulating factor, or macrophage colony-stimulating factor. Macrophage colony cells showed dendritic cell-line morphology and cellular aggregates. IL-13 did not affect granulocyte colony and erythroid burst formation. Delayed addition of IL-13 and replating onto the culture dishes with IL-13 showed that macrophage colony formation was suppressed during days 8 and 14 of culture. These results indicate that IL-13 affects the growth of the late stage of committed macrophage progenitors. Single-cell culture of isolated CD34+CD33+ cells with IL-13 confirmed that macrophage colony formation was significantly suppressed. These results show that IL-13 directly suppresses the proliferation of differentiating macrophages. In addition, these suppressive effects of IL-13 were synergistic with IL-4. Furthermore, in the liquid culture of bone marrow cells in the presence of IL-13, the number of CD14 (monocyte-macrophage antigen)-positive cells decreased and CD18 (LFA-1 beta)-positive cells increased. It is concluded that IL-13 affects the growth of the late stage of macrophage precursors as well as mature monocytes. Induction of differentiation of human monocytes may be correlated with the suppression of their progenitors.
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PMID:Interleukin-13 selectively suppresses the growth of human macrophage progenitors at the late stage. 778 Jan 35

Cellular differentiation is thought to play an important role in the susceptibility of monocytic lineage cells to human immunodeficiency virus (HIV) infection as well as in their ability to support virus replication. In addition, virus replication in monocytes/macrophages has been demonstrated in vitro to be strongly modulated by several cytokines such as tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. The purpose of the present study was to investigate the interaction between cellular differentiation and cytokines in the regulation of HIV expression from chronically infected monocytic lineage cells. U1, a persistently HIV-infected promonocytic cell line, is characterized by low levels of virus expression which can be modulated by several cytokines. 1 alpha,-25-Dihydroxyvitamin D3 (Vit.D3), a well-known differentiating agent for myelomonocytic cells which has been previously reported to modulate HIV replication in other in vitro systems, induced maturation of U1 cells toward a macrophage-like phenotype, as demonstrated by the induction of the differentiation-associated cell surface markers CD14 and CD11b. Vit.D3-induced differentiation did not result in induction of HIV expression; however, when U1 cells were stimulated with tumor necrosis factor alpha in the presence of Vit.D3, a synergistic induction of cell differentiation and viral expression was demonstrated. In contrast, Vit.D3 suppressed the induction of HIV expression in U1 cells stimulated with gamma interferon, interleukin-6, and granulocyte-macrophage colony-stimulating factor, although synergy between Vit.D3 and these cytokines was observed in terms of cellular differentiation. These data suggest that differentiation of monocytic cells does not necessarily correlate with increased HIV expression.
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PMID:Effect of cellular differentiation on cytokine-induced expression of human immunodeficiency virus in chronically infected promonocytic cells: dissociation of cellular differentiation and viral expression. 788 4

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