Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The myeloid-monocytic cells ML-1, HL-60, THP-1, and U-937 were chronically infected (for > 2 years) with the lymphotropic human immunodeficiency virus type 1 (HIV-1) strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1/HIV-1 and HL-60/HIV-1 cells showed a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-1/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers revealed a differential expression of CD4, CD8, CD11c, CD14, CD15, CD20, HLA-DR, and HLA-DQ in non- or chronically infected cells. In chronically infected cells, the steady-state levels for tumor necrosis factor-alpha, interleukin (IL)-1 beta, and granulocyte-macrophage colony-stimulating factor mRNA remained unchanged whereas the one for IL-6 dropped.
 ...
PMID:Characterization of human immunodeficiency virus-1-infected cells of myeloid-monocytic lineage (ML-1, HL-60, THP-1, U-937). 145 15

Human eosinophils are known to lose Ia antigen expression as they mature, and, accordingly, eosinophils obtained from the blood of five eosinophilic donors and three of four normal donors failed to display the major histocompatibility complex class II antigen HLA-DR, as determined by flow cytometry. However, when eosinophils from these nine donors were maintained in culture with recombinant human granulocyte-macrophage colony-stimulating factor and murine 3T3 fibroblasts, HLA-DR consistently developed on the eosinophils. By days 4-6 of culture, 24-97% of eosinophils were HLA-DR+, and the eosinophils remained morphologically mature. In contrast, another class II antigen, HLA-DQ, was not detectable by flow cytometry on eosinophils from eight of nine donors. Cultured eosinophils were able to synthesize HLA-DR, as documented by the incorporation of [35S]methionine into immunoprecipitable HLA-DR heavy and light chains. These findings show that mature eosinophils can synthesize and express HLA-DR and provide a means whereby eosinophils may interact with CD4+ lymphocytes.
 ...
PMID:Mature human eosinophils have the capacity to express HLA-DR. 291 83

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.
 ...
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

The hematopoietic growth factors interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) regulate the survival, maturation, and activation of eosinophils. Corticosteroids in contrast have a negative effect both on the hematopoietic process and the function of eosinophils. We have unexpectedly observed synergy between IL-5 and glucocorticoids such as dexamethasone and hydrocortisone for induction of the MHC class II antigens HLA-DR and HLA-DP on eosinophils isolated from human blood. Similarly glucocorticoids enhanced GM-CSF and IL-3, but not interferon gamma (IFN gamma), induced expression of these antigens. Expression of a third MHC class II molecule, HLA-DQ, was not induced on eosinophils by any of the cytokines alone, but in one of three donors tested, IL-3 plus dexamethasone induced high levels of expression. Although cytokine-induced expression of the accessory molecule intercellular adhesion molecule 1 (ICAM-1) was partially inhibited by glucocorticoids, cytokine- and dexamethasone-treated eosinophils presented antigen more efficiently to a hemagglutinin peptide-specific T-cell clone than eosinophils treated with cytokine alone. These results highlight a potential new role for endogenous or exogenous glucocorticoid hormones in enhancing MHC class II expression by eosinophils.
 ...
PMID:Synergy between dexamethasone and interleukin-5 for the induction of major histocompatibility complex class II expression by human peripheral blood eosinophils. 791 86

The transitional stages in the relationship between sentinel monocytes and messenger dendritic cells that are active in adaptive immunity, are, as yet, unclear. To explore these events, 2-hr adherent peripheral blood mononuclear cells were used either as monocytes, or cultured for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to generate dendritic cells, and the phenotypic features and relationship of the two cell populations was investigated using an extensive panel of monoclonal antibodies (mAbs). The features of the shift from monocyte to dendritic cell were also examined by daily phenotyping during the 7-day culture period. Twenty-five mAbs, most of which recognized known CD molecules, bound both monocytes and dendritic cells equally, whereas 19 mAbs exhibited differential staining. Four molecules not previously reported on dendritic cells were documented: CD87, CD98, CD147 and CD148. Seven cell-surface molecules (HLA-DQ, CD1a, CD13, CD30, CD43, CD63 and CD86) were expressed either at very low levels or not at all on monocytes, but had a strikingly increased expression on dendritic cells, suggesting a role in antigen presentation. The kinetics of monocyte to dendritic cell transition revealed a rapid activation phase within the first 24 hr, with a considerable increase in expression of the activation markers HLA-DR, CD13, CD14 and CD98; this was followed by a down-regulation of CD14 and a more gradual development of the other dendritic cell features over the remaining 6 days, with steady increases in CD1a, CD18, CD43, CD86, HLA-DR and HLA-DQ. Thus, these studies have demonstrated four novel components of the dendritic cell, and have documented the dynamic multistep nature of the process whereby an antigen-presenting dendritic cell phenotype may emerge from a monocyte precursor.
 ...
PMID:From sentinel to messenger: an extended phenotypic analysis of the monocyte to dendritic cell transition. 976 44

Human mast cells (MC) were examined for expression of MHC class II antigens and for their ability to activate CD4+ T cell hybridomas through presentation of superantigen (SAg). HMC-1, a leukemic immature MC line expressing class II Ags, was shown to efficiently present the staphylococcal enterotoxin B (SEB) SAg to responding T cell hybridoma on treatment with interferon-gamma (IFN-gamma), which up-regulated class II molecules. The study was then extended to human normal MC. Almost pure (>99%) cord blood-derived MC (CBMC) were shown to express class II Ags (HLA-DR and HLA-DQ) and CD80, which were up-regulated by IFN-gamma treatment and, to a lesser extent, by interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). CBMC directly activated CD4+ T cell hybridomas through presentation of SEB and TSST1 SAgs. The production of IL-2 required a cell-to-cell contact between T cells and CBMC and it was inhibited by anti-class II antibodies. Furthermore, an additional pretreatment of CBMC by IFN-gamma or GM-CSF or IL-4 had no effect on their presenting efficiency. This previously unknown function of human MC, i.e., MHC class II-dependent activation of CD4+ T cells, may be critical in subsequent cellular activation events because colocalization of mast and T cells is frequently observed at sites of antigen entry.
 ...
PMID:MHC class II-dependent activation of CD4+ T cell hybridomas by human mast cells through superantigen presentation. 1041 Sep 97

Although dendritic cells (DC) can be cultured from cord blood (CB) CD34+ progenitor cells, the generation of DC from CB monocytes has not been reported. In this paper, we explored the generation of DC from CB monocytes to establish the simplest way to obtain a substantial number of DC from CB. We isolated monocytes from CB mononuclear cells (CB-MNC) by the plastic adherence method. These adherent cells (monocyte-rich cells) were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) or in serum-free X-VIVO 15 medium (SFM) for 7 days, both of which contained 100 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) and 10 ng/ml interleukin-4 (IL-4) with or without 10 ng/ml tumor necrosis factor-alpha (TNF-alpha) (added at day 5). In the presence of GM-CSF and IL-4, CB-adherent cells became nonadherent, acquired DC morphology, and showed increased expression of CD1a, CD80, CD86, and HLA-DR; they lost membrane CD14 and some cells with the expression of CD83 and CMRF-44 were generated. With the addition of TNF-alpha to these cultures and culturing for further 2 days, the proportion of CD83+ cells was elevated in both the FBS and SFM culture systems, compared with the culture without TNF-alpha. In the culture with TNF-alpha, cells expressing CD1a, CD80, CD86, HLA-DR, and HLA-DQ were markedly increased. TNF-alpha-treated cells were demonstrated to be stronger stimulators for proliferation of both allogeneic CB lymphocytes and PB lymphocytes than were cells not treated with TNF-alpha. The yield of CD83+ DC at day 7 of cultures was 4.9 +/- 1.1 x 10(5) or 3.0 +/- 0.5 x 10(5) per 1.2 x 10(7) CB-MNC plated initially when cultured in FBS or SFM, respectively. These results have shown that a substantial number of mature DC could be generated from CB-adherent cells even by serum-free culture. We then compared these CB-adherent cell-derived DC (CB-DC) with peripheral blood (PB)-adherent cell-derived DC (PB-DC) in cell-surface phenotype and function. We found day 7 CB-DC have lower expression of CD80, CD1a, CD83, and CMRF-44 than day 7 PB-DC, but CB-DC have a similar capacity to stimulate the proliferation of both allo-CB lymphocytes and PB lymphocytes, compared with PB-DC. CB-DC cultured with GM-CSF and IL-4 have almost identical capacity of phagocytosis to take up fluorescein isothiocyanate (FITC)-dextran and Lucifer yellow (LY), compared with PB-DC. In summary, our findings suggest CB adherent cells, when cultured with GM-CSF, IL-4, and TNF-alpha, are a potent source of functional DC. Thus, CB-DC as well as PB-DC may become valuable tools for immunotherapy.
 ...
PMID:Generation of dendritic cells from adherent cells of cord blood by culture with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha. 1098 43