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)

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been introduced in the treatment of chemotherapy-induced neutropenia. Effects of these CSFs on the cellular immune system were evaluated in 38 neutropenic gynecological cancer patients during chemotherapy. In addition to restoring the leukocyte count, GM-CSF--to a greater extent than G-CSF--also induced neopterin, a sensitive marker of macrophages activated by interferons. This effect was confirmed in vitro by investigating the effects of these CSFs on interferon-gamma-mediated pathways in THP-I human myelomonocytic cells. The results suggest activation of immune effector cells by GM-CSF.
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PMID:Increased production of immune activation marker neopterin by colony-stimulating factors in gynecological cancer patients. 751 25

Bioassay and northern blot analyses revealed that, among several functional murine macrophage (M phi) clones, lipopolysaccharide (LPS) stimulation generated in distinct induction levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF). When compared with these induction profiles, the M phi clones could be classified into two types; G type (G-CSF GM-CSF-M-CSF+) and GM type (G-CSF +/- GM-CSF M-CSF+) of M phi clones. Unlike G-CSF and GM-CSF that were inducible factors, M-CSF mRNA was constitutively expressed without stimulation and was differentially controlled between the G and GM types; LPS induction decreased M-CSF mRNA in the former, but increased it in the latter. Further northern blot analysis revealed that interferon-gamma (IFN-gamma) suppressed constitutive expression of M-CSF mRNA, and that costimulation with both LPS and IFN-gamma reduced expression of G-CSF and M-CSF mRNA in the G type of M phi clone, but induced higher expression of GM-CSF and M-CSF mRNAs in the GM type of M phi clone compared with LPS alone. However, in either case, IFN-gamma completely inhibited LPS-induced production of active CSF of the M phi clones, which was observed even in IFN-gamma pretreatment, and also abrogated autoactivation of GM-CSF. Our present results suggested that murine M phi clones had differentially regulated expression of CSFs and that IFN-gamma had a regulatory function of inhibiting CSF production of murine M phi s.
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PMID:Differential expression of colony-stimulating factor (CSF) in murine macrophage clones: interferon-gamma-mediated inhibition of CSF production. 752 Aug 41

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

The present studies investigated the balance of positive and negative growth signals in direct regulation of hematopoiesis. Interleukin-3 (IL-3) combined with Steel factor (SLF) optimally stimulated proliferation of Lin-Thy-1+ murine bone marrow progenitors in single-cell assays, and that proliferation was inhibited more than 90% by transforming growth factor-beta 1 (TGF-beta 1). Colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1, or IL-6 as a third stimulatory growth factor was incapable of counteracting the TGF-beta 1-mediated inhibition of IL-3-plus-SLF-stimulated growth, while G-CSF slightly enhanced the number of TGF-beta 1-resistant clones. As a fourth factor, only IL-1 could partially overcome the TGF-beta 1-induced growth inhibition. While the presence of a cocktail of five additional stimulatory growth factors did not enhanced the frequency of single Lin-Thy-1+ progenitors proliferating in response to IL-3 plus SLF, the number of responding progenitors in the presence of TGF-beta 1 was enhanced nine-fold. Furthermore, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), but not macrophage inflammatory protein-1 alpha (MIP-1 alpha), cooperated with TGF-beta 1 to reverse the proliferative effects of multiple stimulatory cytokines, resulting in 76% inhibition. Thus, the direct effects of single inhibitory factors on hematopoietic progenitor cell growth can be reversed by multiple stimulatory growth factors, and negative growth factors can directly cooperate to suppress progenitor cell growth stimulated by multiple positive-acting factors.
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PMID:The growth response of Lin-Thy-1+ hematopoietic progenitors to cytokines is determined by the balance between synergy of multiple stimulators and negative cooperation of multiple inhibitors. 752 86

Murine eosinophils express the low-affinity Fc gamma receptors recognized by the monoclonal antibody (mAb) 2.4G2, which are involved in the activation of these cells. We have studied the membrane and RNA expression of the low-affinity Fc gamma receptors on murine eosinophils stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), and interleukin-4 (IL-4). Flow cytometric analysis (FACS) of eosinophils incubated with GM-CSF and IFN-gamma showed an up-regulation on the expression of these receptors with a maximal effect at 24 hr. IL-4 failed to induce any positive or negative effect in these cells. To assess the pattern of expression of the low-affinity Fc gamma receptors on eosinophils, Northern blot analyses were carried out using specific cDNA probes encoding for the Fc gamma RII and Fc gamma RIII. Murine eosinophils constitutively express transcripts for Fc gamma RII and RIII. Incubation with GM-CSF from 3 to 12 hr produced a potent induction of the two transcripts studied (Fc gamma RII and RIII). IFN-gamma did not induce any important up-regulation of the two transcripts from 3 to 12 hr of incubation. By contrast, IL-4 produced a marked inhibition of both transcripts at 24 hr of incubation. Expression of the gamma-chain transcript which is associated with Fc gamma RIII has been detected on freshly isolated eosinophils. This study demonstrates a different regulation pattern of these receptors depending on the cytokine or growth factor used to stimulate murine eosinophils.
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PMID:Modulation of the Fc gamma RII and Fc gamma RIII induced by GM-CSF, IFN-gamma and IL-4 on murine eosinophils. 752 44

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.
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PMID:The functional characterization of interleukin-10 receptor expression on human natural killer cells. 754 68

The addition of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to hormone-dependent cells induces tyrosine phosphorylation of Janus protein kinase 2 (Jak2) and activates its in vitro kinase activity. To explore the role of Jak2 in IL-3/GM-CSF-mediated signal transduction, we constructed a CD16/CD7/Jak2 (CD16/Jak2) fusion gene containing the external domain of CD16 and the entire Jak2 molecule and expressed this fusion protein using a recombinant vaccinia virus. The clustering of CD16/Jak2 fusion protein by cross-linking with an anti-CD16 antibody induced autophosphorylation of the fusion protein but did not induce the phosphorylation of either the endogenous Jak2 or the beta chain. Cross-linking of CD16/Jak2 stimulates the tyrosine phosphorylation of a large group of proteins that are also phosphorylated after the addition of IL-3 or GM-CSF and include proteins of 145, 97, 67, 52, and 42 kDa. Closer analysis demonstrated that the CD16/Jak2 phosphorylates Shc, a 52-kDa protein, and the 145-kDa protein associated tightly with Shc, as well as mitogen-associated protein kinase (pp42). Electrophoretic mobility shift assays demonstrate that CD16/Jak2 activates the ability of signal transduction and activation of transcription (STAT) proteins to bind to an interferon-gamma-activated sequence oligonucleotide in a manner similar to that seen after IL-3 treatment. Cross-linking of the CD16/Jak2 protein stimulated increases in c-fos and junB similar to IL-3 but did not cause major changes in the levels of the c-myc message, which normally increases after IL-3 treatment. Thus, a transmembrane CD16/Jak2 fusion is capable of activating protein phosphorylation and mRNA transcription in a manner similar but not identical to hematopoietic growth factors.
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PMID:Signal transduction by a CD16/CD7/Jak2 fusion protein. 754 2

T cell independent antigens type 2 (TI-2), which are represented predominantly by polysaccharide antigens, stimulate humoral antibody responses in the absence of T-cell help. We and others have recently reported that natural killer cells and/or natural killer cell derived lymphokines may provide a form of 'help' that is necessary for the induction and maintenance of TI-2 responses. Two natural killer cell derived lymphokines, interferon-gamma and granulocyte-macrophage colony-stimulating factor, show synergistic stimulatory activity in inducing Ig secretion in B cells stimulated by a multivalent ligand that mimics TI-2 antigens. The recent finding that natural killer cells have receptors for various classes of polysaccharides supports a role for these cells in regulating responses to TI-2 antigens.
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PMID:T cell independent antigens. 754 99

Freshly isolated peripheral blood neutrophils, unlike monocytes and eosinophils, do not bind interleukin-3 (IL-3) or respond to IL-3). We show that neutrophils cultured for 24 hours in granulocyte-macrophage colony-stimulating factor (GM-CSF) express mRNA for the IL-3 receptor (R) alpha subunit, as shown by RNase protection assays, and IL-3R alpha chain protein, as shown by cytometric analysis using two different specific monoclonal antibodies. This effect was selective for GM-CSF, because granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interferon-gamma, and IL-1 failed to induce the IL-3 receptor. Saturation binding curves with 125I-IL-3 and Scatchard transformation showed the presence of about 100 high-affinity and 4,000 low-affinity receptors. Because neutrophils have been shown to express human leukocyte antigen (HLA)-DR in response to GM-CSF, we examined the possibility that IL-3 could augment HLA-DR expression on GM-CSF-treated cells. We found that neutrophils incubated with 30 ng/mL IL-3 as well as 0.1 ng/mL GM-CSF expressed a mean of 2.1-fold higher levels of HLA-DR than with GM-CSF alone (P < .005), confirming the signaling competence of the newly expressed IL-3R. This increase was seen even at maximal concentrations of GM-CSF and IL-3 can have an additive effect on mature human cells. The augmentation of HLA-DR by IL-3 was specific because it could be inhibited by a blocking anti-IL-3R antibody. Expression of class II molecules by neutrophils under these conditions may have significance for antigen presentation. These results provide further evidence for the role of GM-CSF as an amplification factor in inflammation by inducing neutrophil responsiveness to IL-3 produced by T cells or mast cells.
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PMID:Neutrophils activated by granulocyte-macrophage colony-stimulating factor express receptors for interleukin-3 which mediate class II expression. 757 64

Dendritic cells are the most potent antigen-presenting cells of the immune system. Although dendritic cells are likely to secrete selective cytokines that facilitate antigen presentation, the difficulty in isolating pure dendritic cells in sufficient numbers has made assessment of this function imprecise. In this study, pure populations of CD83+ human blood dendritic cells were isolated by previously established enrichment procedures and subsequent cell sorting. Cytokine gene expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA. Resting CD83+ dendritic cells expressed interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) mRNA, while activation of cells with phorbol myristate acetate induced IL-1 alpha and beta, IL-9, TNF-beta, interferon-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, and G-CSF mRNA expression. Resting CD83+ cells also expressed the Rantes, MCP-1, MIP-1 alpha, and MIP-1 beta chemokines, with 1-309 expression induced upon activation. Resting and activated CD83+ dendritic cells also expressed receptors for IL-2 (CD25), TGF-beta 1 and -beta 3, and GM-CSF as determined by indirect immunofluorescence staining. These results indicate that dendritic cells have the ability to produce a variety of soluble factors which are likely to contribute substantially to the potent allostimulatory activity of these cells.
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PMID:A distinct pattern of cytokine gene expression by human CD83+ blood dendritic cells. 757 30

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