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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 role of CD11/CD18 leukocyte adhesion molecules and their ligands in mediating non-major histocompatibility complex (MHC) restricted lymphocyte cytotoxicity is controversial. In order to examine the role of target cell intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of lymphocyte function-associated antigen (LFA-1) (CD11a/CD18), we exposed the human leukemia cell line, HL-60, to a variety of agents implicated in modulating ICAM-1 expression and/or sensitivity to lymphocyte cytolysis. Exposure of HL-60 cells to retinoic acid (RA), interferon (IFN)-alpha, IFN-beta, and IFN-gamma induced protection from lymphokine-activated killer (LAK) cytolysis. Only RA and IFN-gamma induced ICAM-1 expression. Tumor necrosis factor and vitamin D3, which also induced ICAM-1 expression, increased HL-60 sensitivity to LAK lysis. Granulocyte-macrophage colony-stimulating factor also increased sensitivity to LAK lysis; ICAM-1 was not induced. The state of cellular differentiation and expression of class I and II MHC antigens also did not correlate with sensitivity to LAK cytolysis. Exposure of untreated HL-60 cells and HL-60 cells expressing ICAM-1 to monoclonal antibody (mAb) versus ICAM-1 did not modulate LAK sensitivity. Exposure of LAK cells to mAb versus LFA-1 partially inhibited cytolysis; mAb versus CD18 inhibited cytolysis more completely. HL-60 cells were resistant to natural killer lysis; exposure to the various experimental agents did not alter sensitivity. We conclude that leukemic cell sensitivity to LAK cytolysis can be modulated by a variety of agents. Although our results suggest a role for leukocyte CD11/CD18 adhesion molecules in LAK cytolysis, the poor correlation between ICAM-1 expression and sensitivity to LAK lysis suggest that interactions other than LFA-1/ICAM-1 conjugation may be more central to the processes involved.
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PMID:Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis: role of intercellular adhesion molecule-1. 136 53

We describe dendritic cell progenitors within the CD34+ stem cell compartment in neonatal cord blood and identify growth factors contributing to their differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF), although mainly promoting the growth and differentiation of monocyte-macrophages (mono-m psi s), also induced the differentiation of cells with the distinctive morphological features of dendritic cells (DCs). Tumor necrosis factor (TNF) in combination with GM-CSF promoted further growth of both cell types but most notably increased the DC content. In situ analysis revealed that the cells exhibiting DC morphology were positive for class II major histocompatibility complex antigens but were CD14 negative, did not exhibit nonspecific esterase activity, and were nonphagocytic. Moreover, the mixed leukocyte reaction stimulatory capacity of cultures with the higher DC content was greater. TNF, interleukin-1 (IL-1), IL-6, or platelet-derived growth factor (PDGF) was inactive in promoting stem cell proliferation or DC morphology. IL-1 or PDGF synergized with GM-CSF to increase mono-m psi-associated cell proliferation but did not increase the DC content. The development of a common DC-monocyte precursor was suggested by the presence of colony-forming unit-like clusters containing mono-m psi s and DCs and one sharp proliferative peak. The loss of DC morphology after 21 days, coupled with increases in mono-m psi-associated markers and a constant number of viable cells, further suggests that DC morphology may fluctuate in culture or is a transient feature acquired by certain cells of the mono-m psi lineage.
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PMID:TNF in combination with GM-CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages. 138 91

We have studied the role of murine eosinophils as antigen-presenting cells (APC). Eosinophils have several characteristics that support the hypothesis of its function as potential APC: they have phagocytic capacity, express adhesion molecules and major histocompatibility complex (MHC) class II antigens and can produce and release interleukin-1 (IL-1). We have obtained several T cell clones specific for Mesocestoides corti antigens and used T cell hybridoma specific for ovalbumin (OVA) to test this hypothesis. Granulocyte-macrophage colony-stimulating factor-activated pure eosinophils (99.9%), express class II antigens and are able to present M. corti antigens to specific T cell clones or OVA to T cell hybridoma 3DO 11.10, inducing the proliferation of T cell clones and IL-2 release by the T cell hybridoma. Proliferation of T cells clones is dependent on the number of eosinophils used as APC. We have compared the efficiency of the same number of macrophages and eosinophils as APC, and have found that macrophages are more efficient than eosinophils. Lysosomotropic agents, such as chloroquine and ammonium chloride, that inhibit antigen processing, impaired eosinophil presentation. This presentation is restricted by MHC class II and inhibited by anti-I-Ad monoclonal antibody. The present study provides clear evidence of APC function for eosinophils. Our investigation points to a new role for eosinophils in the immune response.
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PMID:Eosinophil as antigen-presenting cell: activation of T cell clones and T cell hybridoma by eosinophils after antigen processing. 162 30

This study was undertaken in an effort to understand the role of cytokines in T lymphocyte trafficking into inflamed synovium and in the potential enhancement of antigen presentation by human synovial fibroblasts. We found that interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon-gamma (IFN gamma) each increased the cell surface expression of intercellular adhesion molecule 1 (ICAM-1) on human synovial fibroblasts in a dose- and time-dependent manner. Maximal ICAM-1 expression occurred within 8 hours of induction, with the following order of efficacy: IFN gamma greater than TNF alpha greater than IL-1 beta. The number of cells bearing the ICAM-1 antigen also increased, from a basal level of approximately 30% to more than 83% after cytokine induction (for all 3 cytokines). ICAM-1 expression rapidly decreased following cytokine removal. The expression of lymphocyte function-associated antigen 3 was also examined, but it was not changed by any of the 3 cytokines. Class I major histocompatibility complex antigen expression was increased modestly by all 3 cytokines, and expression was maximal by 24 hours after treatment. Only IFN gamma induced HLA class II antigen expression, and this expression persisted for up to 6 days following removal of the lymphokine. IL-6 and granulocyte-macrophage colony-stimulating factor had no effect on any of the parameters examined. Our data support an interactive role for inflammatory cytokines and the expression of adhesion ligands and HLA antigens by human synovial fibroblasts in the pathogenesis of synovial inflammation in rheumatoid arthritis.
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PMID:Role of cytokines in inflammatory synovitis. The coordinate regulation of intercellular adhesion molecule 1 and HLA class I and class II antigens in rheumatoid synovial fibroblasts. 170 92

In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL-10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.
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PMID:Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. 194 Jul 99

Granulocyte-macrophage colony-stimulating factor (GmCSF) is a lymphokine secreted by class II major histocompatibility complex (MHC)-restricted T cells after lectin or antigen stimulation. To investigate the relationship between interleukin-2 (IL-2) and GmCSF production, we utilized long-term cultures of porcine myelin basic protein (PMBP)-specific T helper cell clones that were maintained with IL-2 in the absence of antigen or irradiated antigen-presenting cells (APC). We have found that supernatants of these T cell clones contained GmCSF activity after IL-2 stimulation. Inhibition of cell proliferation by irradiation failed to stop GmCSF production. When these clones were stimulated with PMBP and irradiated APC in the presence of anti-IL-2 receptor antibody, the T cell supernatants still contained GmCSF activity. These results indicate that (1) GmCSF production by T helper clones after IL-2 stimulation is independent of cell proliferation and (2) antigen/MHC-stimulated GmCSF production by T cell clones can occur by an IL-2-independent pathway.
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PMID:Murine T helper cell clones secrete granulocyte-macrophage colony-stimulating factor (GmCSF) by both interleukin-2-dependent and interleukin-2-independent pathways. 252 42

Cytotoxic T-lymphocytes (CTLs) specific for autologous human squamous cell cancer of the lung were generated by stimulation of peripheral blood lymphocytes with autologous tumor cells in vitro. The CTL line was >97% CD3+, CD8+, CD16- and produced tumor necrosis factor-alpha, gamma-interferon, and granulocyte-macrophage colony-stimulating factor after stimulation with autologous tumor. The CTLs lysed autologous tumor but failed to recognize autologous or histocompatibility leukocyte antigen-matched lymphoid cells, K562, or allogeneic tumor cells of several histological types. Antibody-blocking studies suggested that the CTLs recognized one or more antigens presented by the class I major histocompatibility complex molecule Aw68. To characterize these antigens further, histocompatibility leukocyte antigen Aw68 molecules were extracted from the squamous cell cancer of the lung tumor line by immunoaffinity chromatography, and the associated peptides were eluted in acid and separated by reversed-phase high-performance liquid chromatography. Reconstitution of the CTL epitope was evaluated by adding these peptides to autologous Epstein-Barr virus-transformed B-cells. Two peaks of reconstituting activity were observed, suggesting that these CTLs recognize at least two Aw68-associated peptides. This study confirms the existence of a CTL response against autologous human squamous cell cancer of the lung and suggests that this CTL response is directed against peptide epitopes presented by the class I major histocompatibility complex molecules. It is anticipated that this approach will permit identification of peptide epitopes for lung cancer-specific CTLs.
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PMID:Cytotoxic T-lymphocyte response to autologous human squamous cell cancer of the lung: epitope reconstitution with peptides extracted from HLA-Aw68. 751 55

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

The human interleukin-3 (IL-3) receptor is constitutively expressed on certain hematopoietic cells where it mediates proliferation and differentiation, or functional activation. We have recently found that human umbilical vein endothelial cells (HUVECs) also express IL-3 receptors and that the expression is enhanced by stimulation with the monokine tumor necrosis factor alpha. In this report we show that the lymphokine interferon gamma (IFN gamma) is a powerful stimulator of the IL-3 receptor of HUVECs and that the combination of IL-3 and IFN gamma has a synergistic effect on major histocompatibility complex (MHC) class II expression and on the production of the early-acting hematopoietic cytokines IL-6 and granulocyte colony-stimulating factor (G-CSF). IFN gamma caused a time- and dose-dependent up-regulation of mRNA for both the alpha and beta chains of the IL-3 receptor, with maximal effects occurring 12 to 24 hours after stimulation with IFN gamma at 100 U/mL. Induction of mRNA correlated with protein expression on the cell surface, as judged by monoclonal antibody staining of both receptor chains and by the ability of HUVEC to specifically bind 125I-labeled IL-3 (125I-IL-3). Scatchard analysis of HUVECs stimulated with IFN gamma at 100 U/mL for 24 hours showed approximately 6,300 IL-3 receptors per cell that were of a high affinity class (dissociation constant [kd] = 500 pmol/L) only. The addition of IL-3 to IFN gamma-treated HUVECs strongly enhanced the expression of MHC class II antigen. Importantly, IFN gamma and IL-3 also exhibited a synergistic effect in the induction of the mRNA for G-CSF and IL-6. This was reflected in increased amounts of G-CSF and IL-6 protein in HUVEC supernatants. In contrast, IFN gamma and IL-3 did not stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-8 production in HUVECs. These results show that IFN gamma is a strong stimulator of IL-3 receptor expression in HUVECs and suggest that in vivo T-cell activation, causing the concomitant production of IFN gamma and IL-3, may lead to enhanced endothelial MHC class II expression and to the selective production of early-acting hematopoietic cytokines. Thus, IL-3 could influence immunity and hematopoiesis by acting not only on hematopoietic cells, but also on vascular endothelium.
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PMID:Interferon-gamma upregulates interleukin-3 (IL-3) receptor expression in human endothelial cells and synergizes with IL-3 in stimulating major histocompatibility complex class II expression and cytokine production. 754 Aug 83

Recent immunomorphological studies have demonstrated the presence of distinct populations of resident tissue macrophages and major histocompatibility complex (MHC) class II+ dendritic cells within tissues lining the anterior chamber of rat, mouse and human eyes. The location of these cells in sites of potential contact with the aqueous humour-filled anterior chamber suggests that either of these cells may perform a role in immunosurveillance of this 'immune-privileged site'. The aim of the present study was to isolate highly purified dendritic cells and tissue macrophages from enzymatically disaggregated rat irides and to compare their relative capacity to stimulate unprimed T lymphocytes in vitro in a mixed leucocyte reaction assay. Dendritic cells freshly isolated from iris tissue exhibited a moderate ability to stimulate unprimed T lymphocytes. However, following 48 hr of culture in granulocyte-macrophage colony-stimulating factor (GM-CSF)-supplemented medium, MHC class II+ dendritic cells demonstrated a markedly enhanced stimulatory capacity that was identical to that of Langerhans' cells isolated from skin. Tissue macrophages isolated from rat iris, however, demonstrated little allostimulatory capacity, either when freshly isolated or following 48 hr of culture in GM-CSF. This study provides the first definitive evidence that MHC class II+ cells within tissues lining the anterior chamber are functionally equivalent to dendritic cells described in other tissues. These findings have important implications for our understanding of the mechanisms of immune surveillance within the anterior chamber of the eye.
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PMID:Functional studies of major histocompatibility class II-positive dendritic cells and resident tissue macrophages isolated from the rat iris. 755 59


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