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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 human recombinant interleukin-2 (IL-2) and human recombinant granulocyte-macrophage colony-stimulating factor on the growth of a virulent strain of Escherichia coli in tissue culture medium and in untreated, normal mouse serum was investigated. Both of these cytokines enhanced the growth of the microorganism two- to threefold in tissue culture medium with or without additional fetal calf serum and in untreated mouse serum. IL-4 did not have any effect on the growth of this microbe under the conditions tested. That the enhancement of growth seen with recombinant IL-2 was due to the active cytokine was shown by the following data: (i) addition of an antibody to IL-2 abrogated the growth-promoting effect; (ii) the excipient buffer, which contained everything except the active cytokine, was inactive in modifying bacterial growth; and (iii) heat-inactivated recombinant IL-2 did not promote enhanced microbial growth. The enhancement of growth with IL-2 was significant with concentrations as low as 1 U/ml. Growth of an avirulent strain of E. coli was not stimulated by IL-2. Moreover, addition of IL-2 to growth virulent E. coli in tissue culture medium led to rapid removal of the cytokine from the medium. Collectively, these data suggest that cytokines may act as growth factors for some virulent bacteria.
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PMID:Interleukin-2 and granulocyte-macrophage colony-stimulating factor stimulate growth of a virulent strain of Escherichia coli. 201 45

The effect of a single whole-blood transfusion on the cascade of cytokine secretion was studied in patients with chronic renal failure. The results indicate that 1 week after blood transfusion, no significant changes were observed in the secretion of interleukin-2, colony-stimulating factor, tumor necrosis factor, and gamma-interferon. However, 2 weeks after blood transfusion, a sharp decrease was observed in the generation of these cytokines. A decrease of about 70% was observed in interleukin-2, tumor necrosis factor, and gamma-interferon secretion. The production of colony-stimulating factor 2 weeks after blood transfusion amounted to about 30% less than baseline levels. No statistical differences in interleukin-1 production were observed throughout the study. In addition, we found that the decrease in cytokine secretion was paralleled by a sharp increase in the in vitro secretion of prostaglandin E2. Thus the beneficial effect of blood transfusion on graft survival might be due in part to an immunosuppressive effect brought about by immunoregulatory changes via the cascade of cytokine secretion.
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PMID:The effect of a single whole-blood transfusion on cytokine secretion. 211 Sep 41

Lymphokine-dependent T cell proliferation is regulated in part by the cell surface expression of high affinity interleukin-2 receptors (IL-2R). The functional, high affinity form of the IL-2 receptor is comprised of two ligand binding components, IL-2R alpha (Tac, p55) and IL-2R beta (p70/75). In the absence of the other subunit, IL-2R alpha and IL-2R beta bind ligand with only low or intermediate affinity, respectively. The inducible and transient expression of IL-2R alpha regulates the display of high affinity receptors, while IL-2R beta appears to contribute importantly to growth signal transduction. Although the primary structure of both receptor chains has now been elucidated, the mechanism of growth signal transduction through the high affinity IL-2R remains undefined. Of note, IL-2R beta belongs to a novel family of cytokine receptors including the binding proteins for IL-3, IL-4, IL-6, erythropoietin, and granulocyte-macrophage colony-stimulating factor. These various receptors may well utilize a common intracellular signalling pathway.
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PMID:The human interleukin-2 receptor: insights into subunit structure and growth signal transduction. 212 4

Although the fetus is considered to be an "allograft" there is little information concerning the role of lymphokines in human pregnancy. Lymphokines are polypeptides secreted by stimulated lymphocytes that direct the immune response by enabling immune effector cells to communicate with each other. To characterize lymphokine production during normal human pregnancy, we isolated peripheral leukocytes and decidual lymphocyte-like cells from women undergoing repeat cesarean section at term. After stimulation with mitogen and paternal antigen for 24 hours, culture supernatants were assayed for granulocyte-macrophage colony-stimulating factor and interleukin-2 by enzyme-linked immunosorbent assay. There was no difference in the amount of interleukin-2 produced by stimulated peripheral and decidual cells. However, granulocyte-macrophage colony-stimulating factor production by stimulated decidual lymphocyte-like cells was significantly greater than granulocyte-macrophage colony-stimulating factor produced by peripheral lymphocytes. Decidual lymphocyte-like cells produced granulocyte-macrophage colony-stimulating factor both spontaneously and after stimulation with mitogen or paternal antigen, whereas peripheral leukocytes did not. This suggests that the decidua constitutes a distinct immunologic microenvironment.
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PMID:Lymphokine production during term human pregnancy: differences between peripheral leukocytes and decidual cells. 225

The expression of the gene encoding the granulocyte-macrophage colony-stimulating factor (GM-CSF) is induced upon activation of T cells with phytohemagglutinin and active phorbolester and upon expression of tax1, a transactivating protein of the human T-cell leukemia virus type I. The same agents induce transcription from the interleukin-2 receptor alpha-chain and interleukin-2 genes, depending on promoter elements that bind the inducible transcription factor NF-kappa B (or an NF-kappa B-like factor). We therefore tested the possibility that the GM-CSF gene is also regulated by a cognate motif for the NF-kappa B transcription factor. A recent functional analysis by Miyatake et al. (S. Miyatake, M. Seiki, M. Yoshida, and K. Arai, Mol. Cell. Biol. 8:5581-5587, 1988) described a short promoter region in the GM-CSF gene that conferred strong inducibility by T-cell-activating signals and tax1, but no NF-kappa B-binding motifs were identified. Using electrophoretic mobility shift assays, we showed binding of purified human NF-kappa B and of the NF-kappa B activated in Jurkat T cells to an oligonucleotide comprising the GM-CSF promoter element responsible for mediating responsiveness to T-cell-activating signals and tax1. As shown by a methylation interference analysis and oligonucleotide competition experiments, purified NF-kappa B binds at positions -82 to -91 (GGGAACTACC) of the GM-CSF promoter sequence with an affinity similar to that with which it binds to the biologically functional kappa B motif in the beta interferon promoter (GGGAAATTCC). Two kappa B-like motifs at positions -98 to -108 of the GM-CSF promoter were also recognized but with much lower affinities. Our data provide strong evidence that the expression of the GM-CSF gene following T-cell activation is controlled by binding of the NF-kappa B transcription factor to a high-affinity binding site in the GM-CSF promoter.
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PMID:NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene. 240 68

Febrile reactions often occur in cancer patients given various biological response modifiers such as alpha- or gamma-interferon or interleukin-2. The present studies were undertaken to determine the effects of moderately elevated temperatures (39 degrees C) on various immunological functions related to host defense against malignant cells. The production of the cytokines interleukin-1, interleukin-2, erythroid burst-promoting activity, and granulocyte-macrophage colony-stimulating factor from activated human mononuclear cells was assessed in vitro at 34, 37, and 39 degrees C and found to be reduced at 39 degrees C. The natural killer activity of human mononuclear cells preincubated for 18 h at various temperatures was also significantly reduced (P less than 0.001) at 39 degrees C. Although the addition of recombinant interleukin-1-beta, interleukin-2, and alpha-interferon during the 18-h incubation augmented natural killer activity at all temperatures, the enhancing effects were least apparent at 39 degrees C. Indomethacin increased cytokine-primed natural killer cell activity at all temperatures but did not reverse the inhibitory effects of elevated temperatures. These results suggest that the fever associated with treatment with pyrogenic cytokines may partially offset the direct stimulatory effects of these substances on cellular immune function.
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PMID:Inhibitory effects of elevated temperature on human cytokine production and natural killer activity. 243 Jun 93

An overview of the immune system is presented, and the pathogenesis, transmission, diagnostic tests, diagnosis, immunotherapy, and vaccine development for human immunodeficiency virus (HIV) are reviewed. More than 42,000 cases of acquired immunodeficiency syndrome (AIDS) have now been reported in the United States, and an additional 250,000 cases are expected by 1991. The immunopathogenesis of HIV infection involves both cellular and humoral components of the immune system, with a characteristic depletion of helper T lymphocytes, impaired delayed hypersensitivity, and polyclonal B-cell activation. Monocytes and macrophages are also infected, and these cells provide a transport mechanism into the central nervous system. HIV is transmitted primarily by sexual, blood, and perinatal mechanisms. Enzyme-linked immunosorbent and Western blot assays are used in diagnostic tests, and diagnosis of AIDS is based on the presence of secondary infection or tumor at least moderately indicative of cellular immune deficiency in the absence of predisposing factors. Three approaches are being tested for treating HIV infection: immunomodulators, vaccines, and antiviral agents. Immunomodulators--including interferons, interleukin-2, immune reconstitution with bone-marrow transplantation and lymphocyte transfusions, transfer factor, granulocyte-macrophage colony-stimulating factor, inosine pranobex (isoprinosine), and naltrexone--are being tested with no great successes. Various approaches to vaccine development, including genetically engineered subunit proteins, synthetic peptides, and infectious recombinant viruses, are being considered. Primary immune responses do result from at least one vaccine. Future studies will evaluate combination approaches to therapy. HIV infections confront the health-care system with a serious challenge. It is too early to assess the effectiveness of the various therapeutic strategies for immune deficiencies caused by HIV.
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PMID:Current concepts in clinical therapeutics: immunologic treatment of human immunodeficiency virus infections. 244 17

Highly purified natural killer (NK) cell suspensions were tested for their capacity to release colony-stimulating activity (CSA) in vitro. NK cell suspensions comprised primarily CD16+ cells and were devoid of CD3+ T cells, CD15+ monocytes, and of B cells. CSA was detected in the NK cell supernatants and sustained the growth of myeloid colonies from both normal peripheral blood and bone marrow. CSA could be in part inhibited by pretreating NK cell culture supernatants with a specific goat anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antiserum. The inhibition, however, was never complete, a finding that suggests that additional factors were responsible for CSA. Incubation of NK cells with K562 cells (an NK-sensitive target) or with normal bone marrow cells resulted in the appearance of a strong colony-inhibiting activity (CIA) in the culture supernatants. Such CIA was demonstrable in an experimental system where bone marrow or peripheral blood progenitors were induced to form myeloid colonies in the presence of conditioned medium by CSA-producing giant cell tumor (GCT) cells. Stimulation of NK cells with NK-insensitive targets failed to induce CIA production. Neutralizing antitumor necrosis factor (TNF) monoclonal antibodies (MoAbs) were found capable of inhibiting CIA present in the supernatants of NK cells stimulated with K562 cells. Following treatment with anti-TNF antibodies, CSA was again detectable in the same supernatants. This finding indicates that induction of TNF production did not concomitantly switch off CSA production by NK cells. Pretreatment of NK cells with recombinant interleukin-2 (rIL-2) or gamma interferon (r gamma IFN) did not change the amount of CSA released. However, treatment with rIL-2 caused the appearance of a factor in the NK cell supernatants capable of sustaining the formation of colonies of a larger size.
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PMID:Production of colony-stimulating activity by human natural killer cells: analysis of the conditions that influence the release and detection of colony-stimulating activity. 250

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

Quiescent T cells can be induced to express many genes by mitogen or antigen stimulation. The messenger RNAs of some of these genes undergo relatively rapid degradation compared to messenger RNAs from constitutively expressed genes. A T cell activation pathway that specifically regulates the stability of messenger RNAs for the lymphokines interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor is induced by stimulation of the CD28 surface molecule. This pathway does not directly affect the steady-state messenger RNA level, transcription, or messenger RNA half-life of other T cell activation genes, including c-myc, c-fos, IL-2 receptor, and the 4F2HC surface antigen. These data show that stimuli received at the cell surface can alter gene expression by inducing specific changes in messenger RNA degradation.
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PMID:Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. 254 May 28


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