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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 effects of normal bone marrow fibroblasts (BM FB) on proliferation and differentiation of 10 myeloid leukemic cell lines were investigated in a serum-free co-culture system. The proliferation of three of the cell lines was supported by BM FB. Three of the myeloid cell lines were inhibited 40-70%. The co-culture supernatants were tested for the secretion of hematopoietic cytokines by bioassays. Except for IL-6, which was already produced constitutively by BM FB, only little amounts of interleukin-1 (IL-1), granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) could be detected in several co-culture supernatants. It could be shown that, according to cytologic and functional criteria, the myeloid leukemic cell lines ML-2 and PLB-985 differentiate along the monocyte-macrophage pathway after co-culture with BM FB. They revealed a histiocytic phenotype and could be induced to produce reactive oxygen intermediates (ROI) after stimulation with zymosan or phorbol-myristate-acetate (PMA). Additional proof for differentiation was obtained from flow cytometric analysis of surface differentiation antigens and adhesion molecules. The neutralization of IL-6 activity in the co-cultures by antibodies resulted in prevention of differentiation of PLB-985 cells, while differentiation of ML-2 cells in the co-cultures was not affected by addition of anti-IL-6 antibodies. Furthermore, in co-culture experiments with fibroblasts from skin and foreskin, we found a differentiation of PLB-985 cells comparable to that in co-cultures with BM FB, but poor differentiation of ML-2 cells. These data suggest that different mechanisms are involved in the differentiation of ML-2 and PLB-985 cells.
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PMID:Effects of bone marrow fibroblasts on the proliferation and differentiation of myeloid leukemic cell lines. 749 67

Mature blood neutrophils have a short lifespan in vitro and are not easily transfectable. We obtained terminally mature neutrophils after differentiation of immature transfectable PLB-985 myeloid cells by treatment with dimethylformamide (0.5%), Nutridoma SP (1%) and fetal calf serum (0.5%). Maturation was shown by functional degranulation, in response to bacterial N-formyl peptide (fMLP), of specific granules and secretory vesicle contents; the latter emerge during the last step of normal neutrophil differentiation into bone marrow. These differentiated cells also produced quantities of superoxide anion similar to those produced by blood neutrophils, in response to physiological stimuli (fMLP); in addition, the fMLP-induced respiratory burst was primed by the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor. Thus, in our experimental conditions, PLB-985 cells transformed into fully differentiated neutrophils capable of fine regulation by inflammatory agents. This cell model will help in the understanding of the molecular mechanisms underlying neutrophil functions.
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PMID:Differentiation of PLB-985 myeloid cells into mature neutrophils, shown by degranulation of terminally differentiated compartments in response to N-formyl peptide and priming of superoxide anion production by granulocyte-macrophage colony-stimulating factor. 1202 49

The interleukin 4 (IL-4)/IL-4 receptor (IL-4R) system in promyelocytes is not well documented. Here, we used promyelocytic leukaemia PLB-985 cells differentiated with dimethylsulfoxide (PLB-985D) toward neutrophil-like phenotype to investigate the IL-4/IL-4R system. PLB-985 cells did not express CD132 (gammac) but expressed the complete IL-4 type II receptor (IL-4Ralpha and IL-13Ralpha1). Moreover, PLB-985 cells lost surface expression of IL-13Ralpha1 during differentiation, resulting in PLB-985D cells expressing only IL-4Ralpha fully responsive to IL-4, as judged by activation of mitogen-activated protein (MAP) kinases and Janus kinase 1. IL-4 also increased suppressor of cytokine signalling 3 (SOCS3) protein level in the presence of the proteasome inhibitor MG132 exclusively in PLB-985D cells. As the IL-4Ralpha chain has been associated with a component of the phagocyte NADPH oxidase, we used PLB-985-gp91(phox) deficient cells (mimicking chronic granulomatous disease, X-CGD), to investigate the IL-4/IL-4R system in X-CGD-D cells. IL-4 was found to activate MAP kinases in X-CGD-D cells but did not up-regulate SOCS3, in contrast to granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and IL-6. Utilization of catalase, cycloheximide and genistein inhibitors showed that IL-4 induced SOCS3 by a mechanism dependent on a complete NADPH oxidase complex, protein synthesis and tyrosine phosphorylation, but independent of production of reactive oxygen species. We conclude that IL-4 induces cell signalling in promyelocytes expressing only IL-4Ralpha.
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PMID:Investigation of the interleukin (IL)-4/IL-4 receptor system in promyelocytic leukaemia PLB-985 cells during differentiation toward neutrophil-like phenotype: mechanism involved in IL-4-induced SOCS3 protein expression. 1800 66