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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)

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and HTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-1 alpha, IL-1 beta and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.
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PMID:Expression of cytokine mRNA in leukemic cells from adult T cell leukemia patients. 250 74

The susceptibilities of human blood monocytes and alveolar macrophages (AM) to cytotoxicity mediated by lymphokine (IL-2)-activated killer (LAK) cells were examined. Monocytes and AM of healthy donors were obtained by counter-flow centrifugal elutriation (CCE) and bronchoalveolar lavage, respectively. The LAK activity induced by incubation of blood mononuclear cells (MNC) for 4 days with recombinant interleukin 2 (IL-2) was measured by a 4-h 51Cr release assay. The LAK cells were not cytotoxic to freshly isolated monocytes, but were cytotoxic to autologous fresh AM and monocytes that had been incubated for more than 4 days in medium alone. Blood monocytes that had been incubated for 4 days in medium with granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) or interleukin 3(IL-3) were much more susceptible than untreated monocytes to the cytotoxicity of LAK cells. When blood monocytes were separated by CCE into subpopulations of three sizes (small, medium and large), the medium- and large-sized monocytes showed greater responses to GM-CSF in terms of DNA synthesis and colony formation than the small-sized cells. After treatment with GM-CSF for 4 days, these medium and large monocytes were more susceptible than the small monocytes to the cytotoxic action of LAK cells. These results suggest that LAK cells may be important in situ in down-regulating the functions of mature macrophages and blood monocytes that have responded to GM-CSF.
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PMID:Killing of alveolar macrophages and of monocytes that have responded to granulocyte-macrophage colony-stimulating factor by human lymphokine-activated killer cells. 250 89

1. Colony-stimulating factor (CSF-1) was isolated from a large volume of fresh normal human urine by 5 steps of purification and enrichment. 2. The purification factor is 100,000 fold and the purified compound exhibits a 2.16 x 10(7) U/mg of protein sp. act. 3. The isolated CSF-1 is a sialoglycoprotein with 41.5% of carbohydrate. The almost complete removal of this carbohydrate moiety (up to 91%) was achieved by incubation with trifluoromethane sulfonic acid. 4. The deglycosylated CSF-1 (DG-CSF-1) possesses an apparent Mr 38,000 compared to native CSF-1 with an initial Mr 57,000 (Goa et al., 1988). 5. The features of the interaction of radio-iodinated [125I]CSF-1 with single cell suspensions from various human tissues (bone marrow, spleen, blood, peritoneal cavity, alveolar lavage, lymph node and thymus), were studied. 6. The binding activity of peritoneal macrophages was the highest among the cells examined and erythrocytes, thymus and blood granulocytes showed no CSF-1 binding. 7. On incubation with [125I]CSF-1 at 0 degrees C, cellular binding of [125I]CSF-1 reached a stable maximum within 16 hr. This is in contrast to the association behaviour at higher temperature. 8. At 37 degrees C, cellular associated [125I]CSF-1 levels reached, within 90 min, an unstable maximum which was up to 10 times less than that occurring under the same conditions at 0 degree C. From the Scatchard plot analysis, we obtained the affinity constant and the number of receptor(s). 9. The binding site is sensitive to trypsin. 10. The receptor alone, (labelled by cross-linking to [125I]CSF-1 with di-succinylimidyl-suberate), is a polypeptide with an approx. Mr 110,000. 11. Our results showed that the receptor of CSF-1 is a tyrosin-kinase.
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PMID:The specific binding activities of human urinary radioiodinated colony-stimulating factor-1 to various human tissue cells. 252 35

There are different types of myeloid leukemic cells that can be induced to differentiate to mature granulocytes or macrophages by different hematopoietic regulatory proteins. One type of leukemic clone can be induced to differentiate by recombinant macrophage and granulocyte differentiation-inducing protein-type 2 (MGI-2), which we have shown is Interleukin-6 (IL-6), and another type of leukemic clone can be differentiated by recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3. There was no subpopulation of growth factor-responsive or differentiation-defective cells before induction of differentiation in either type of clone. In both clones, induction of differentiation-induced requirement for a hematopoietic protein for cell viability. Viability of the cells was maintained by IL-6, IL-3, or macrophage colony-stimulating factor (M-CSF) but not by GM-CSF in the cells differentiated by IL-6, and by GM-CSF or IL-3 but not by IL-6 or M-CSF in the cells differentiated by GM-CSF or IL-3. The viable cells with a differentiated phenotype continued to multiply. In undifferentiated leukemic cells with no or few surface receptors for some of these proteins, there was an upregulation of the number of receptors during differentiation for the proteins to which the cells responded. But there were also differentiating leukemic cells with an upregulation of GM-CSF receptors although GM-CSF could not maintain the viability of the differentiating cells. The results indicate that induction of hormone responsiveness and upregulation of the hormone receptors can both occur in differentiating leukemic cells, and that the regulation of these two events can be separated.
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PMID:Induction of dependence on hematopoietic proteins for viability and receptor upregulation in differentiating myeloid leukemic cells. 254 28

Previous in vitro investigations on enriched human hematopoietic progenitors have led to the conclusion that the purified recombinant multipoietins, interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can alone induce the formation of colonies from a variety of multipotent and lineage committed progenitors. Since fetal calf serum was included in these cultures and itself might contain growth factors or other cofactors, we re-examined the actions of the CSFs in serum-deprived conditions. Results show that both the multipoietins are inadequate stimuli of colony formation. At maximal concentrations IL-3 alone induces only 25% of the granulocyte and macrophage colony-forming units (CFU-G and CFU-M) produced by a T-cell conditioned medium that contains a mixture of CSFs. When IL-3 was added at the initiation of the cultures and erythropoietin (ep), G-CSF, or M-CSF added on day 3, almost full recovery of erythroid, granulocytic, and monocytic colonies, respectively, was obtained. Similar results were obtained with GM-CSF except that fewer erythroid colonies were recovered at high concentrations, and almost maximal CFU-M proliferation could be induced. These results show that in serum-deprived conditions, the multipoietins must be combined with lineage specific CSFs for full progenitor expression.
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PMID:Combinations of recombinant colony-stimulating factors are required for optimal hematopoietic differentiation in serum-deprived culture. 264 85

It is clear from extensive in vitro data that different subsets of lymphocytes stimulate and inhibit the growth of hematopoietic stem and progenitor cells. In order to clarify the complexity of the network between regulatory lymphocytes and hematopoietic target cells, we have examined the stimulatory and inhibitory effects derived from different lymphoid subsets. The regulatory influence of lymphocytes is transmitted mainly through the release of cytokines including the interleukins, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-beta and the interferons, all of which have non-specific effects on a variety of hematopoietic cells. Since these cytokines amplify the effects of other, more lineage-specific cytokines (e.g., erythropoietin, thrombopoietin and granulocyte or macrophage colony-stimulating factor) on the proliferation and differentiation of progenitor cells, the present review supports the conclusion that lymphoid subsets play a critical role in ensuring an optimal hematopoietic response to specific demands.
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PMID:Lymphoid cell regulation of hematopoiesis. 264 74

In vitro culture of either human peripheral blood monocytes or murine peritoneal macrophages for 72 hr in the presence of macrophage colony-stimulating factor (M-CSF) dramatically increased their subsequent ability to mediate antibody-dependent cellular cytotoxicity (ADCC). The M-CSF-treated cells were more effective in ADCC at lower effector to target cell ratios and in the presence of lower concentrations of tumor-specific monoclonal antibody than the untreated control cells. Two other hematopoietic cytokines, granulocyte-macrophage colony-stimulating factor and interleukin-3, reported to enhance other macrophage effector functions were ineffective in promoting the development of ADCC by cultured human monocytes. All three hematopoietic growth factors were capable of enhancing the ability of the cultured monocytes to secrete TNF alpha; however, TNF alpha is unlikely to be an important cytotoxic factor in ADCC because neutralizing antibodies against TNF alpha had no affect on ADCC in vitro. Further, much higher concentrations of M-CSF were required to augment monocyte TNF alpha release (20-100 ng/ml) than ADCC capacity (1-10 ng/ml). These results suggest that M-CSF administration might prove effective in increasing the tumoricidal activities of tumor-specific monoclonal antibodies by enhancing the capacity of monocytes and macrophages to mediate ADCC.
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PMID:Macrophage colony-stimulating factor enhances monocyte and macrophage antibody-dependent cell-mediated cytotoxicity. 264 26

In order to maintain adequate circulating numbers of blood cells, the bone marrow must produce billions of cells each day and must be able to rapidly increase production by 10-20-fold in response to infection and hemorrhage. The existence of circulating factors that regulate this process has been suspected for over 100 years. Recently, the genes encoding these growth factors were cloned and their functions are now identified. Interleukin-3 (IL-3) acts on the most primitive hematopoietic stem cell, driving this self-renewing cell to produce progeny of all hematopoietic lineages. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the granulocyte-macrophage progenitor cell, as well as cells committed to the erythroid lineage, to differentiate. G-CSF and M-CSF stimulate the most differentiated myeloid progenitors to produce granulocytes and monocytes/macrophages, respectively. Erythropoietin stimulates the differentiation of late erythroid progenitors. In the lymphoid progenitor lineage, IL-2 stimulates T cell differentiation; IL-4 and IL-6 stimulate differentiation of B cells. The colony-stimulating factors also enhance function and cause activation of the mature cells whose production they induce. In clinical trials, these hormones have successfully ameliorated anemia in renal failure, chronic disease, and in prematurity. They have improved pancytopenias in aplastic anemia, myelodysplastic syndromes, and congenital cytopenias, and they have hastened recovery from chemotherapy and bone marrow transplantation.
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PMID:Hematopoietic hormones: from cloning to clinic. 267 59

Northern blot analysis has identified granulocyte macrophage colony stimulating factor (GM-CSF) mRNA in monocytes and both GM-CSF and interleukin-3 (IL-3) mRNA in lymphocytes. However, these results have not addressed whether all cells or a subset of the population is capable of hematopoietic growth factor (HGF) production. To resolve this question, we applied in situ hybridization of radiolabeled antisense RNA probes to centrifuged preparations of total blood mononuclear cells (BMCs) and fractionated lymphocyte subpopulations. Without stimulation, no circulating cells expressed detectable levels of GM-CSF or IL-3 mRNA. On stimulation of BMCs with phorbol myristate acetate (PMA) and phytohemagglutinin or PMA and the calcium ionophore ionomycin, approximately 5% expressed GM-CSF mRNA and approximately 1% IL-3 mRNA. Control sense probes produced no labeled cells. To determine the subsets of lymphocytes capable of GM-CSF and IL-3 expression, BMCs were fractionated by FACS into CD8+ and CD4+ lymphocyte subsets and CD16+ (NK) cells. The unfractionated cells and cell fractions were then stimulated with PMA and ionomycin. Results demonstrated that 3% to 5% of the CD16+, CD8+, and CD4+ lymphocytes produced GM-CSF mRNA. However, the number of IL-3 mRNA-positive cells in the FACS-sorted subsets was greatly reduced (0.02% to 0.05%) as compared with the unseparated cells (1%). Treatment of BMCs with high-dose interleukin-2 (IL-2) for 1 week followed by PMA plus ionomycin resulted in a lymphocyte population in which 50% and 3% of cells expressed GM-CSF and IL-3 mRNA, respectively. Thus, GM-CSF and IL-3 mRNA expression in T cells and NK cells is restricted to a small fraction of cells that can be greatly expanded by IL-2 stimulation. These results suggest a possible physiologic mechanism for increasing HGF production by circulating lymphocytes.
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PMID:Granulocyte-macrophage colony-stimulating factor and interleukin-3 mRNAs are produced by a small fraction of blood mononuclear cells. 267 15

Colony-stimulating factors (CSFs) are pivotal for proliferation and function of hematopoietic cells. We found that lymphotoxin, a product of activated lymphocytes, stimulates accumulation of granulocyte-macrophage (GM)-CSF and macrophage (M)-CSF proteins and mRNAs in fibroblasts. An increase in GM- and M-CSF mRNA levels occurred within 2 hours after addition of 1,000 U/mL lymphotoxin and levels plateaued over the next 24 hours. Tumor necrosis factor alpha (TNF alpha) was about five times more potent than lymphotoxin at low concentrations, and was nearly 1.5 to to 2 times more potent at maximally stimulating concentrations of the cytokines. Stimulation by lymphotoxin did not require either new protein synthesis or protein kinase-C stimulation. Stability studies of GM- and M-CSF transcripts in fibroblasts showed that M-CSF mRNA was five times more stable (half-life [t 1/2], 100 minutes) than GM-CSF mRNA (t 1/2, 20 minutes). Stability of these mRNAs was unchanged after stimulation of the cells with lymphotoxin. In addition, exposure of cells to 12-O-tetradecanoylphorbol 13-acetate did not alter stability of M-CSF mRNA but markedly prolonged the stability of GM-CSF mRNA. This is consistent with data showing that the AT-rich consensus region in the 3' untranslated region of many transiently expressed cytokines including GM-CSF but not M-CSF, play a major role in their mRNA stability. Our results suggest that activated lymphocytes can affect hematopoietic cell function and growth by stimulating production of CSFs by mesenchymal cells.
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PMID:Lymphotoxin: stimulation and regulation of colony-stimulating factors in fibroblasts. 267 16


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