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)

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.
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PMID:MHC class II-dependent activation of CD4+ T cell hybridomas by human mast cells through superantigen presentation. 1041 Sep 97

Inhibitory receptors originally identified in natural killer (NK) cells have also been detected in other leukocyte types, thus suggesting that they may play a more general role in the control of leukocyte function. Here we report data on p75/adhesion receptor molecule 1 (AIRM1), a surface inhibitory receptor of the sialoadhesin family originally identified in NK cells that is also expressed by normal and leukemic myeloid cells. Given the homology between p75/AIRM1 and CD33, we also reanalyzed CD33, a major myeloid marker of still unknown function. We discuss recent data indicating that engagement of p75/AIRM1 or CD33 sharply inhibits the in vitro proliferation/differentiation of CD34+ myeloid precursors induced by stem cell factor and granulocyte-macrophage colony-stimulating factor. Importantly, a similar in vitro inhibitory effect occurs in monocyte/macrophages as well as in chronic or acute myeloid leukemias. While CD33 appears to act via the induction of apoptosis, p75/AIRM1 blocks cell proliferation but does not appear to induce apoptosis. A synergistic effect in the induction of apoptosis has also been documented between antibodies specific for CD33 and the chemotherapic agent etoposide. Taken together, the use of appropriate ligands against CD33 or p75/AIRM1 may represent a new therapeutic tool for treatment of myeloid leukemias or diseases characterized by overwhelming macrophage activation.
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PMID:p75/AIRM1 and CD33, two sialoadhesin receptors that regulate the proliferation or the survival of normal and leukemic myeloid cells. 1151 47

An unusual CD18 monoclonal antibody (mAb) MEM-148 binds, in contrast to standard CD18 mAbs, specifically to peripheral blood monocytes and neutrophils activated by various stimuli such as phorbol myristate acetate, opsonized zymosan, heat-aggregated immunoglobulin, and (after priming with lipopolysaccharide, tumor necrosis factor, or granulocyte-macrophage colony-stimulating factor) also by formyl-methionyl-leucyl-phenylalanine. In addition, in vivo activated neutrophils obtained from urine of patients following recent prostatectomy were also strongly positive for MEM-148. On the activated myeloid cells the mAb recognized a 65- to 70-kd protein identified immunochemically and by mass spectrometric peptide sequencing as a membrane-anchored fragment of CD18 (the common chain of leukocyte integrins) produced by proteolytic cleavage. The CD18 fragment originated mainly from integrin molecules stored intracellularly in resting cells, it was unassociated with CD11 chains, and its formation was inhibited by several types of protease inhibitors. Thus, the 65- to 70-kd CD18 fragment represents a novel abundant activation marker of myeloid cells of so far unknown function but possibly involved in conformational changes in leukocyte integrin molecules resulting in increased affinity to their ligands.
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PMID:A proteolytically truncated form of free CD18, the common chain of leukocyte integrins, as a novel marker of activated myeloid cells. 1152 Aug 8

RUNX1, or AML1, is a transcription factor that is the most frequent target for chromosomal gene translocations in acute leukemias. RUNX1 is essential for definitive hematopoiesis in embryos and profoundly influences adult steady-state hematopoiesis both positively and negatively. To investigate this wide range of normal activities and the pathological role of RUNX1, it is important to define the functions of different domains of the protein. RUNX1, RUNX2, and RUNX3 are highly conserved in their DNA binding runt homology domain and contain divergent sequences of unknown function N-terminal to this domain. Here we analyzed the role of the N-terminal sequence and the alpha-helix of the runt homology domain of Runx1 in DNA binding, transactivation, and megakaryocytopoiesis. Both the N terminus and the alpha-helix were found to reduce DNA binding of Runx1 and be essential for transactivation of the granulocyte-macrophage colony-stimulating factor and Ialpha1 promoters by Runx1. The N terminus of Runx1, including the alpha-helix, was also required for transactivation of a Gal4 reporter when expressed as fusion proteins with a Gal4 DNA binding domain, and the N terminus alone was capable of stimulating transcription when fused to the Gal4 DNA binding domain. The N terminus and the alpha-helix, however, were not required for megakaryocyte development from embryonic stem cells differentiated in vitro. Thus, our findings define a second transactivation domain of Runx1 that is differentially required for activation of transcription of some Runx1-dependent promoters and megakaryocytopoiesis.
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PMID:Identification of an N-terminal transactivation domain of Runx1 that separates molecular function from global differentiation function. 1680 98