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)

The combined use of zidovudine (ZDV) and interferon (IFN) alfa-2a has been shown to have antiretroviral and antitumor potential benefit in the treatment of acquired immune deficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). However, the clinical use of this combination is frequently complicated by the overlapping myelotoxicity of these agents. We report here the results of a phase I/II study in which granulocyte-macrophage colony-stimulating factor (GM-CSF) was used for those KS patients who became neutropenic while receiving ZDV (1,200 mg/d) and IFN (9 x 10(6) U/d). Nineteen of 29 patients (66%) developed an absolute neutrophil count (ANC) of less than 1,000 cells per cubic millimeter and were begun on GM-CSF. All experienced a prompt increase in the ANC. Those patients receiving GM-CSF/ZDV/IFN alfa-2a had an improved end of study ANC when compared with the ZDV/IFN alfa-2a group, but did not have an increased rate of tumor response, end of study CD4 cell count, or improvement in any other hematologic variable. The use of GM-CSF was not associated with increased toxicity and, in particular, was not associated with a change in serum human immunodeficiency virus (HIV) p24 antigen. Tumor response was noted in 50% of the assessable patients (33% overall) despite "high-risk" characteristics in 80%. Of the responding patients, seven were on GM-CSF and might have otherwise required an alteration in ZDV/IFN alfa-2a dose level. Further study of GM-CSF as an alternate to dose modification of this (ZDV/IFN alfa-2a) and other combination therapies for AIDS patients is warranted.
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PMID:Granulocyte-macrophage colony-stimulating factor mitigates the neutropenia of combined interferon alfa and zidovudine treatment of acquired immune deficiency syndrome-associated Kaposi's sarcoma. 196 May 65

Therapy with antilymphocyte globulin (ALG) has been shown to be effective in restoring hematopoiesis to some patients with aplastic anemia. It would be useful to have a method for predicting those likely to be responders versus nonresponders. The mode of immunostimulatory action of ALG is of interest in addition to its immunosuppressive action. We examined in vitro the distribution of the proliferative responses of ALG-stimulated peripheral blood mononuclear cells (PBMCs) obtained from 18 patients with aplastic anemia, eight of whom responded to ALG and 10 who did not. We found a significant difference in the proliferative response of PBMCs obtained from the eight responders versus the 10 nonresponders (P less than .01). Two-color flow cytometry analysis of the patients' PBMCs stimulated by ALG in vitro showed that the CD4-positive subsets were activated to a greater extent by ALG than the CD8-positive subsets. Moreover, a positive correlation with the clinical response of patients to ALG with granulocyte-macrophage colony-stimulating factor produced by their PBMCs stimulated by ALG suggests that the immunostimulatory property of ALG has an important role in the treatment of aplastic anemia. Our results suggest that the clinical response to ALG therapy is correlated with its lymphocyte proliferative effect in vitro, and indicates that the assessment of the proliferative response of PBMCs in vitro would be useful in predicting the clinical response to ALG therapy.
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PMID:Correlation of response of aplastic anemia patients to antilymphocyte globulin with in vitro lymphocyte stimulatory effect: predictive value of in vitro test for clinical response. 202 81

In the present study, culture supernatants from larger granular lymphocytes (LGL) that were activated with Candida albicans antigens were shown to stimulate the ability of neutrophils to inhibit fungal growth. Identification of the activation factors showed that granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor, was involved. Human peripheral blood mononuclear cells were fractionated by Percoll density centrifugation and each subpopulation of cells was stimulated with C albicans yeast cells. GM-CSF was produced in those fractions enriched for LGL, but not T lymphocytes or adherent monocytes. Additionally, the phenotype of the GM-CSF-producing cell was found to be CD2+, CD16+, HLA-DR+, and negative for CD4, CD8, and CD15. Kinetic studies demonstrated that GM-CSF appeared in the supernatants within 2 days of culture and continued to be produced up to 7 days. Optimal stimulation of LGL was seen at a ratio of 3 heat-killed C albicans yeast cells per LGL. Thus, LGL play an important role in host defense against this opportunistic pathogen by producing cytokines, including GM-CSF, which in turn activates the fungicidal activity of neutrophils.
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PMID:Production of granulocyte-macrophage colony-stimulating factor by large granular lymphocytes stimulated with Candida albicans: role in activation of human neutrophil function. 202 83

We describe the unique characteristics of leukaemic basophils from a patient with chronic myelogenous leukaemia (CML). The leukaemic cells were immature basophil-like blasts and expressed CD4, CD7 and HLA-DR in addition to CD13 and CD33. Both immunoglobulin and T cell receptor genes were retained in germline configurations. Interleukin-1 (IL-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as IL-3 or IL-4 enhanced the proliferation and differentiation of leukaemic cells and only basophils were generated from in vitro culture. These results suggest that basophil progenitors expressing CD4, CD7 and HLA-DR may be involved in the development of basophilic crisis of CML and that both IL-1 and GM-CSF may act on basophil progenitors as well as IL-3 or IL-4.
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PMID:Characterization of leukaemic basophil progenitors from chronic myelogenous leukaemia. 204 82

In this report it is shown by immunofluorescence analysis, biochemical analysis and mRNA hybridization that human eosinophils express surface CD4 and interleukin-2 receptor (IL-2R) (CD25) when exposed to eosinophil activators granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3. Although the functional role of eosinophil CD4/CD25 expression has to be elucidated, it will be of interest in further studies to investigate whether in vivo induction of these molecules occurs in association with certain disease processes such as the hypereosinophilic syndrome or in immunological responses during allergic and helminthic parasitic diseases.
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PMID:Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce surface expression of interleukin-2 receptor p55-chain and CD4 by human eosinophils. 219 16

Monocyte/macrophages (M/M) are an important target cell for human immunodeficiency virus (HIV) infection in the body. The study of HIV infection in these cells, however, is rather complicated because they represent a variable population, and because HIV entry and replication in M/M may be markedly influenced by a number of factors. These must be considered in therapeutic approaches to HIV infection. In the present set of experiments, we studied the interaction between certain agents which increase the infection of monocyte/macrophages (M/M) by HIV and two groups of anti-HIV agents: dideoxynucleosides and specific inhibitors of gp120-CD4 binding. We found that the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which markedly enhances HIV replication in M/M, does not affect the activity of recombinant soluble CD4 (sCD4) or OKT4A, two agents which block gp120-CD4 binding. However, it had varying effects on different dideoxynucleosides: GM-CSF increased the net anti-HIV activity of 3'-azido2',3'-dideoxythymidine (AZT), while at the same time it reduced the activity of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). These effects probably represent an interplay between varying effects of GM-CSF on drug entry and phosphorylation. In additional experiments, we showed that very low concentrations of anti-HIV antibodies could enhance HIV infection of the U937 monocytoid cell line. Interestingly, while this effect has been hypothesized to occur through a CD4-independent mechanism, we found that the anti-HIV activities of both sCD4 and OKT4A were unchanged under conditions of enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ability of anti-HIV agents to inhibit HIV replication in monocyte/macrophages or U937 monocytoid cells under conditions of enhancement by GM-CSF or anti-HIV antibody. 222 41

A total of 121 human T-cell clones were raised from nine Mycobacterium bovis BCG-vaccinated healthy individuals. Three clones were autoreactive, 74 responded to BCG in the presence of antigen-presenting cells, and the others required in addition exogenous interleukin 2. Only one clone was CD8+ CD4-, and the rest were CD4+ CD8-. Testing with a panel of mycobacteria suggested that the clones were recognizing epitopes of varied specificity. Out of 44 clones tested, 15 were specific to BCG and Mycobacterium tuberculosis, 22 showed limited cross-reactivity, and 8 were broadly cross-reactive. None of the 22 BCG responder clones could differentiate between Danish, French, Prague, and Moreau strains of BCG. BCG and M. tuberculosis H37Rv also paralleled very closely; however, 6 of 18 BCG- and M. tuberculosis H37Rv-responding clones did not proliferate to Mycobacterium africanum. BCG- and M. tuberculosis H37Rv-specific as well as cross-reactive T-cell clones could be induced to produce interleukin 2, gamma interferon, and granulocyte-macrophage colony-stimulating factor activity.
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PMID:Mycobacterium bovis BCG-induced human T-cell clones from BCG-vaccinated healthy subjects: antigen specificity and lymphokine production. 242 49

Lymphokine gene expression was examined in a panel of 116 short-term murine T-lymphocyte clones derived by single-cell micromanipulation from allogeneic mixed leukocyte cultures. About 30% of clonable T cells, including both CD4+ CD8- and CD4- CD8+ cells, could be expanded for assay at an average of 22 days after cloning. By RNA blot-hybridization analysis, most clones (85-96%) expressed detectable granulocyte-macrophage colony-stimulating factor, interleukin 3, and gamma interferon mRNAs, and 11% expressed interleukin 4 mRNA. Although no differences were noted between CD4+ and CD8+ clones in the combinations of lymphokines produced, CD4+ clones on average transcribed and secreted higher levels. When the frequencies of coexpression of any pair of lymphokine mRNAs were determined, all were found to correspond to the values predicted for random assortment of the individual frequencies. For example, among 13 interleukin 4-positive clones, 11 also transcribed gamma interferon, giving the frequency of double-positive clones expected for random association (9.6% versus 10.8%). Therefore, expression of the four lymphokine genes segregated independently among the clones and did not allow the division of T cells into subsets with distinct patterns of lymphokine synthesis.
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PMID:Coexpression of granulocyte-macrophage colony-stimulating factor, gamma interferon, and interleukins 3 and 4 is random in murine alloreactive T-lymphocyte clones. 246 63

In this study we show that bone marrow macrophages (BMM phi), derived by culturing bone marrow stem cells in macrophage colony-stimulating factor (M-CSF)-containing medium, and activated by an optimal dose of interferon-gamma, selectively interacted with only some out of a group of protein antigen-specific T cell clones as measured by antigen-specific T cell proliferation. Antibody inhibition experiments employing monoclonal anti-CD4 antibodies suggest that the failure of various T cell lines to cooperate with BMM phi might be due to a low avidity of the interaction between these T cells and the accessory cells. We further show that BMC that were allowed to mature in the presence of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) developed into highly efficient accessory cells leading to antigen-specific activation of all T cell clones tested. No correlation was found with the level of expression of MHC class II genes induced in GM-CSF-treated BMM phi, although significant amounts of transcripts of A alpha, A beta and of the non MHC-encoded invariant gamma-chain were detected by Northern blot analysis.
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PMID:Induction of antigen presentation capacity and MHC class II gene expression in bone marrow macrophages derived from GM-CSF-supplemented in vitro cultures. 246 53

The membrane molecule CD4 (L3T4) is thought to facilitate activation of Class II H-2-restricted T cells by binding to Ia determinants on antigen-presenting cells. Recent reports suggest that CD4 can also contribute to antigen-independent activation by anti-T cell receptor (TCR) antibodies. An assay which measures the secretion of two lymphokines, granulocyte-macrophage colony-stimulating factor and interleukin 3 (IL-3), by single T cells activated with an anti-TCR antibody, F23.1, was used to analyze the effects of anti-CD4 antibodies on antigen-independent T cell activation. Single cells of a CD4+F23.1+ clone were micromanipulated into wells to which F23.1 had been immobilized, and their lymphokine secretion was measured 24 hr later. The frequency of lymphokine-secreting cells was consistently reduced up to 10-fold in the presence of soluble anti-CD4 antibody (GK1.5) but only up to 2.5-fold by an antibody to the cell adhesion molecule, LFA-1. In both bulk and single-cell cultures, responses to suboptimal concentrations of F23.1 were more susceptible to inhibition by GK1.5 than responses to optimal F23.1. The failure of GK1.5 to inhibit IL-2-stimulated lymphokine synthesis in bulk cultures suggested that CD4 ligation did not deliver a negative signal to the clone. By contrast, when either anti-CD4 or anti-LFA-1 was immobilized on the same surface as F23.1, the frequency of lymphokine-secreting cells could be increased up to 10-fold. It is concluded that anti-CD4 antibodies can act directly on the responding T cell to affect TCR-dependent activation, in the absence of interaction with antigen-presenting cells or any other cell type.
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PMID:The role of CD4 in antigen-independent activation of isolated single T lymphocytes. 290 16


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