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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)

Human erythroid burst-promoting activity (BPA) of recombinant growth factors and crude materials, of media conditioned by omentum tissue (OMCM), and of media conditioned by the bladder carcinoma cell line (HTB9CM) was measured by three different culture methods. Using the two-stage culture method, significant activity was shown in OMCM (137%-329% of the control), HTB9CM (102%-333%), recombinant human (rh) granulocyte-macrophage colony-stimulating factor (rhGM-CSF) (179%-220%), rh interleukin 3 (rhIL-3) (232%-676%), and rh insulin-like growth factor 1 (rh IGF-1) (106%-175%), whereas there was no significant increase in the number of erythroid bursts by the same additives when the one-stage culture or the delayed erythropoietin method was employed. Linear dose-response curves were observed in the tested range of rhIL-3 and rhGM-CSF. We also observed that 1) a larger amount of rhGM-CSF was required for the optimal stimulation of erythroid burst-forming units (BFU-E) than for the optimal stimulation of granulocyte-macrophage colony-forming units (CFU-GM), and 2) even the maximum dose of rhGM-CSF increased erythroid bursts to a lesser extent than was possible by the addition of rhIL-3. The former results implies that BPA is not the major activity of GM-CSF, and the latter result, although it is not conclusive, suggests that the GM-CSF-responsive BFU-E represent only a subset population of BFU-E responsive to IL-3. The two-stage culture is a useful assay method for screening BPA in biological materials with respect to accuracy, dose responsiveness, and reproducibility.
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PMID:Three quantitative assays for human erythroid burst-promoting activity of recombinant growth factors and of omentum-conditioned medium. 240 58

Febrile reactions often occur in cancer patients given various biological response modifiers such as alpha- or gamma-interferon or interleukin-2. The present studies were undertaken to determine the effects of moderately elevated temperatures (39 degrees C) on various immunological functions related to host defense against malignant cells. The production of the cytokines interleukin-1, interleukin-2, erythroid burst-promoting activity, and granulocyte-macrophage colony-stimulating factor from activated human mononuclear cells was assessed in vitro at 34, 37, and 39 degrees C and found to be reduced at 39 degrees C. The natural killer activity of human mononuclear cells preincubated for 18 h at various temperatures was also significantly reduced (P less than 0.001) at 39 degrees C. Although the addition of recombinant interleukin-1-beta, interleukin-2, and alpha-interferon during the 18-h incubation augmented natural killer activity at all temperatures, the enhancing effects were least apparent at 39 degrees C. Indomethacin increased cytokine-primed natural killer cell activity at all temperatures but did not reverse the inhibitory effects of elevated temperatures. These results suggest that the fever associated with treatment with pyrogenic cytokines may partially offset the direct stimulatory effects of these substances on cellular immune function.
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PMID:Inhibitory effects of elevated temperature on human cytokine production and natural killer activity. 243 Jun 93

Myeloid and erythroid progenitor cells were enriched from human marrow by selecting CD34-positive (CD34 + ve) cells, labeled with the My10 (HPCA-1) antibody, using a fluorescence-activated cell sorter. Seventy-one percent of CD34 + ve cells were blasts and most of these were too primitive to be identified by standard morphological criteria. On average, 9.5% of CD34 + ve cells formed clones after 14 days of culture in semisolid medium supplemented with erythropoietin and medium conditioned by 5637 bladder carcinoma cells. Over 2.5% of CD34 + ve cells were day-14 myeloid colony-forming cells and 2.4% were erythroid colony (burst)-forming progenitors. The remaining progenitors formed myeloid and erythroid clusters. A subpopulation of day-14 myeloid colony-forming cells failed to respond to recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) after accessory cells were removed during enrichment, so it appears that this factor can induce myeloid growth indirectly as well as directly. Recombinant human GM-CSF also supported erythroid colony-formation in cultures of CD34 + ve cells, which suggests that this hemopoietin may act directly on erythroid progenitors.
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PMID:Enrichment of CD34 (My10)-positive myeloid and erythroid progenitors from human marrow and their growth in cultures supplemented with recombinant human granulocyte-macrophage colony-stimulating factor. 245 55

The effects of transforming growth factor beta 1 or beta 2 (TGF-beta 1 or -beta 2) on the in vitro proliferation and differentiation of normal and malignant human hematopoietic cells were studied. Both forms of TGF-beta suppressed both the normal cellular proliferation and colony formation induced by recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the presence of GM-CSF or IL-3, optimal concentrations of TGF-beta (400 pmol/L) inhibited colony formation by erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor cells by 90% to 100%, whereas granulocyte or monocyte cluster formation was not inhibited. In contrast, neither form of TGF-beta had any effect on G-CSF-induced hematopoiesis. The suppressive action appeared to be mediated directly by TGF-beta since antiproliferative responses were also observed in accessory cell-depleted bone marrow cells. In contrast to normal bone marrow cells, both GM- and G-CSF-induced proliferation of cells from patients with chronic myelogenous leukemia were suppressed in a dose-dependent manner by TGF-beta. Differential effects of TGF-beta on the proliferation of established leukemic lines were also observed since most cell lines of myelomonocytic nature studied were strongly inhibited where erythroid cell lines were either insensitive or poorly inhibited by TGF-beta. These results suggest that TGF-beta is an important modulator of human hematopoiesis that selectively regulates the growth of less mature hematopoietic cell populations with a high proliferative capacity as opposed to more differentiated cells, which are not affected by TGF-beta.
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PMID:Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro. 246 Jan 53

Recombinant human interleukin 3 (IL3) produced in Escherichia coli was purified and its activities examined in cultures of highly enriched human bone marrow progenitor cells. Human IL3 stimulated multipotential (CFU-GEMM) and erythroid (BFU-E) progenitor cells, generating 95% more BFU-E than recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). No further enhancement of BFU-E or CFU-GEMM occurred when IL3 and GM-CSF were used in combination. Human IL3 was more effective than GM-CSF in stimulating granulocyte-macrophage colony-forming cells (CFU-GM) in short-term suspension cultures, but did not induce an increase of CFU-GM, BFU-E, or CFU-GEMM above input levels. IL3 was more active on day-14 (d14) than on d7 CFU-GM, similar to GM-CSF, but generated fewer and smaller CFU-GM-derived clones than either GM-CSF or granulocyte CSF (CI-CSF). The simultaneous addition of plateau levels of IL3 and GM-CSF resulted in an infra-additive augmentation of d7 and d14 CFU-GM-derived clones, whereas IL3 and G-CSF enhanced the number and cellularity predominantly of d14 CFU-GM. In liquid cultures, IL3 induced a greater than 100-fold increase in the number of basophil-mast-like cells and eosinophils and allowed maintenance of these cultures for up to 7 weeks. Human GM-CSF was an almost equally potent, stimulus of eosinophil development but had only a marginal effect on basophilic precursors, whereas G-CSF lacked both activities. Therefore, human IL3 is a multilineage hemopoietic growth factor whose activities appear to encompass and extend beyond those of GM-CSF.
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PMID:Stimulation of human hematopoietic progenitor cell proliferation and differentiation by recombinant human interleukin 3. Comparison and interactions with recombinant human granulocyte-macrophage and granulocyte colony-stimulating factors. 246 33

The proliferative effects of recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in semi-solid and liquid cultures of purified CD34+ hematopoietic cells obtained from umbilical cord blood. No important differences in overall cloning efficiencies in response to IL-3 or GM-CSF were observed in semi-solid medium in the presence of erythropoietin (Ep). However, GM-CSF was less effective for the development of erythroid bursts (BFU-E), and only IL-3 was observed to induce significant numbers of mixed-erythroid colonies (E-MIX). Both IL-3 and GM-CSF also induced proliferation of CD34+ in liquid cultures. Proliferative responses to IL-3 were found to be more rapid and stronger than to GM-CSF, although the number of initial responsive cells as judged by autoradiography were comparable. Enhanced proliferation of CD34+ cells both in semi-solid and liquid cultures was obtained in the presence of combinations of IL-3 and GM-CSF. The responses observed were less than additive, with the exception of the development of eosinophil colonies and clusters, where IL-3 and GM-CSF were found to act synergistically. In secondary cultures, proliferative responses to GM-CSF were strongly enhanced by preculture of CD34+ cells in IL-3 for four to 11 days, and to a lesser extent by preculture in GM-CSF. Finally, responses to IL-3 were not affected by preculture of CD34+ cells in the presence of GM-CSF. Our results indicate that there is a wide overlap of cells capable of proliferating either in response to IL-3 or to GM-CSF within the cord blood CD34+ compartment. However, differences in primary proliferation kinetics and increased responsiveness to GM-CSF following preculture suggest the importance of a sequential action of IL-3 and GM-CSF in the expansion of CD34+ cells.
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PMID:Combined and sequential effects of human IL-3 and GM-CSF on the proliferation of CD34+ hematopoietic cells from cord blood. 246 3

Sublethally irradiated CBA/J mice injected with lymph node cells (LNC) of C3H/He mice exhibit aplastic anemia within 3 weeks. Aplastic anemia plasma (AAP) from these mice was found to inhibit granulocyte-macrophage colony (GM-CFU) formation. This inhibitory action was not strain specific and was not generated in donor:host combination involving other strains. AAP also inhibited the formation of colonies derived from leukemic cell lines. Though this activity inhibited GM-CFU, it did not affect erythroid colony formation. Two experiments were performed to examine the mechanism of inhibition. Superoptimal concentrations of recombinant mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) did not reverse AAP-induced inhibition of colony formation. Bone marrow cells preincubated with AAP for 24 h and washed were unchanged in their ability to form GM-CFU colonies. Thus, the inhibitory activity acted neither as a competitive nor a cytotoxic agent. Interferons and certain prostaglandins, known to inhibit colony formation, were not found in active concentrations in AAP. The inhibitory activity of AAP was heat stable, nondialyzable, inextractable with chloroform, precipitable with 50% ammonium sulfate, and had a molecular weight of 100,000 daltons. In contrast, control plasma from mice given only sublethal irradiation and injected with saline had significantly less inhibitory activity, which was not heat stable and was extractable with chloroform. Thus, LNC in certain host mouse strains generate a plasma activity that can inhibit the formation of normal and leukemic GM-CFU colonies.
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PMID:Inhibitor of granulocyte-macrophage colony formation in plasma of mice rendered aplastic by allogeneic lymph node cells. 246 13

We have attempted to evaluate in vivo effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on acute radiation hematopoietic injury in mice. BDF1 mice, irradiated with 7.5-Gy x-rays, were injected i.p. twice daily for 10 days with 10(5) U recombinant human G-CSF, 3.75 x 10(5) U recombinant murine GM-CSF, or a combination of both. G-CSF significantly enhanced the recovery of not only peripheral leukocytes but also platelets and hematocrit on days 14 and 21 after irradiation. GM-CSF significantly enhanced the recovery of platelets on day 14 and peripheral leukocytes on day 21. G-CSF markedly enhanced the recovery of spleen colony-forming units (CFU-S), colony-forming units in culture (CFU-C), erythroid burst-forming units (BFU-E), and megakaryocyte colony-forming units (CFU-Meg) both in bone marrow and in the spleen. GM-CSF significantly enhanced the recovery of CFU-Meg in bone marrow on day 14. We found synergistic effects between G-CSF and GM-CSF on CFU-S, CFU-C, and CFU-Meg in the spleen on day 14, although we found antagonistic effects between G-CSF and GM-CSF on CFU-S and CFU-C in bone marrow on day 7, and on platelet counts on day 7. These results indicate that the administration of recombinant G-CSF and GM-CSF may be useful in accelerating hematopoietic recovery in patients with acute radiation hematopoietic injuries.
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PMID:Effects of recombinant granulocyte colony-stimulating factor (rG-CSF) and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on acute radiation hematopoietic injury in mice. 247 60

We report that highly purified human platelet factor 4 (PF4) inhibits human megakaryocytopoiesis in vitro. At greater than or equal to 25 micrograms/ml, PF4 inhibited megakaryocyte colony formation approximately 80% in unstimulated cultures, and approximately 58% in cultures containing recombinant human IL 3 and granulocyte-macrophage colony-stimulating factor. Because PF4 (25 micrograms/ml) had no effect on either myeloid or erythroid colony formation lineage specificity of this effect was suggested. A synthetic COOH-terminal PF4 peptide of 24, but not 13 residues, also inhibited megakaryocyte colony formation, whereas a synthetic 18-residue beta-thromboglobulin (beta-TG) peptide and native beta-TG had no such effect when assayed at similar concentrations. The mechanism of PF4-mediated inhibition was investigated. First, we enumerated total cell number, and examined cell maturation in control colonies (n = 200) and colonies (n = 100) that arose in PF4-containing cultures. Total cells per colony did not differ dramatically in the two groups (6.1 +/- 3.0 vs. 4.2 +/- 1.6, respectively), but the numbers of mature large cells per colony was significantly decreased in the presence of PF4 when compared with controls (1.6 +/- 1.5 vs. 3.9 +/- 2.3; P less than 0.001). Second, by using the human leukemia cell line HEL as a model for primitive megakaryocytic cells, we studied the effect of PF4 on cell doubling time, on the expression of both growth-regulated (H3, p53, c-myc,and c-myb), and non-growth-regulated (beta 2-microglobulin) genes. At high concentrations of native PF4 (50 micrograms/ml), no effect on cell doubling time, or H3 or p53 expression was discerned. In contrast, c-myc and c-myb were both upregulated. These results suggested the PF4 inhibited colony formation by impeding cell maturation, as opposed to cell proliferation, perhaps by inducing expression of c-myc and c-myb. The ability of PF4 to inhibit a normal cell maturation function was then tested. Megakaryocytes were incubated in synthetic PF4, or beta-TG peptides for 18 h and effect on Factor V steady-state mRNA levels was determined in 600 individual cells by in situ hybridization. beta-TG peptide had no effect on FV mRNA levels, whereas a approximately 60% decrease in expression of Factor V mRNA was found in megakaryocytes exposed to greater than or equal 100 ng/ml synthetic COOH-terminal PF4 peptide. Accordingly, PF4 modulates megakaryocyte maturation in vitro, and may function as a negative autocrine regulator of human megakaryocytopoiesis.
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PMID:Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide. 252 11

Marrow progenitor cells from 14 myelodysplastic (MDS) patients and 17 normal donors were assayed in semisolid cultures supplemented with increasing doses of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or medium conditioned by 5637 bladder carcinoma cells (5637CM). At doses of supplements shown to be optimal for colony formation in cultures of normal marrow, myeloid (day 14) colony numbers were subnormal in 10 of 14 MDS marrows cultured in 5637CM and in 8 of 14 cultures containing rhGM-CSF (2.5 ng/ml). However, a high dose of rhGM-CSF (20 ng/ml) raised myeloid colony numbers in cultures of many MDS marrows, so that 9 of 14 now yielded colonies within the normal range; increased levels of 5637CM failed to do this. Erythroid colony growth was poor in 13 of 14 MDS marrow cultures supplemented with erythropoietin in addition to 5637CM or rhGM-CSF. High concentrations of rhGM-CSF did not increase erythroid growth. These data suggest that myeloid progenitors from the MDS clone may have a decreased responsiveness to hemopoietins which can be overcome at high concentrations of growth factors.
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PMID:In vitro growth of myeloid and erythroid progenitor cells from myelodysplastic patients in response to recombinant human granulocyte-macrophage colony-stimulating factor. 264 75


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