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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 hemopoietic growth factors interleukin-3 (IL-3, multi-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) belong to a family of secreted glycoproteins that stimulate the proliferation and differentiation of hemopoietic progenitor cells. IL-3 and GM-CSF have overlapping biological activities and show similar regulation of expression after mitogenic or antigenic stimulation of T lymphocytes. In the present work we have derived a map of the region covering the Il-3 and Csfgm loci using a combination of pulsed-field gel electrophoresis and molecular cloning. The two genes are shown to be 14 kbp apart, in the same orientation with the IL-3 gene 5' of the GM-CSF gene. The proximity of the two genes, together with similarities in their structure, function, and regulation, suggests that they may have arisen by ancient gene duplication.
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PMID:Fine-structure mapping of the murine IL-3 and GM-CSF genes by pulsed-field gel electrophoresis and molecular cloning. 267 40

Colony-stimulating factor 1 is a hematopoietic growth factor that increases 1000-fold in the uteri of pregnant mice, and its receptor is abundantly expressed in the human placenta. The concentration of colony-stimulating factor 1 in amniotic fluid at 33 to 40 weeks (9.0 +/- 1.1 ng/ml) was twofold higher than that at 16 to 18 weeks gestation (4.1 +/- 0.5 ng/ml), whereas maternal serum colony-stimulating factor 1 levels did not rise significantly. Colony-stimulating factor 1 was detected in endometrial extracts from pregnant women and levels were higher than those in extracts from nonpregnant women.
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PMID:Accumulation of colony-stimulating factor 1 in amniotic fluid during human pregnancy. 278 29

T-cell activation induces expression of the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). To define the molecular events involved in the induction of GM-CSF gene expression more clearly, we prepared and analyzed deletion mutants of GM-CSF promoter recombinant constructs. The results localized inducible expression to a 90-base-pair region (-53 to +37) which is active in uninfected and human T-cell leukemia virus-infected T-cell lines but not in resting or mitogen-stimulated B cells. DNase I footprinting experiments revealed protection of sequences contained within this region, including a repeated nucleotide sequence, CATT(A/T), which could serve as a core recognition sequence for a cellular transcription factor. Upstream of these GM-CSF promoter sequences is a 15-base-pair region (-193 to -179) which has negative regulatory activity in human T-cell leukemia virus-infected T cells. These studies revealed a complex pattern of regulation of GM-CSF expression in T cells; positive and negative regulatory sequences may play critical roles in controlling the expression of this potent granulopoietin in the bone marrow microenvironment and in localized inflammatory responses.
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PMID:Characterization of the human granulocyte-macrophage colony-stimulating factor promoter region by genetic analysis: correlation with DNase I footprinting. 283 38

We have recently shown that Abelson murine leukemia (A-MuLV) virus can transform cells in large mixed colonies to give tumorigenic myeloid cell lines capable of autonomous growth in vitro. Initial studies revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) production was consistently activated in these cells. Using a sensitive S1 RNA mapping technique and additional bioassays, we have now obtained evidence of expression of other hemopoietic growth factor genes. Uniformly 32P-labeled, single-stranded DNA probes (greater than 4 x 10(8) cpm/micrograms) were generated for interleukin 3 (IL-3) and GM-CSF using pTZ based vectors. IL-3 mRNA was detected in four of four cloned transformants (from two different infections) at approximately 1% of the level seen in pokeweed mitogen (PWM)-stimulated spleen cells. GM-CSF mRNA was detected in the two clones that showed the highest IL-3 mRNA levels. Medium conditioned by these cells was able to stimulate IL-3-dependent 32D cells, and IL-3- and GM-CSF-dependent B6SUtA cells, and also supported the growth of a variety of single and multilineage colonies in assays of mouse marrow cells even in the presence of neutralizing antibodies to GM-CSF. Rearrangements of the IL-3 and GM-CSF genes were not apparent by Southern blot analysis. Additional bioassays revealed the presence of two other growth factors: IL-6 (hybridoma growth factor or Ifn-beta 2) assayed on B13.29 cells, a factor-dependent murine B-cell hybridoma; and a new pre-B-cell stimulatory factor different from any of the above. Elucidation of the mechanism underlying this phenomenon may provide important insights into the regulation of hemopoietic growth factor gene expression and the role such genes play in human leukemogenesis.
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PMID:Activation of multiple hemopoietic growth factor genes in Abelson virus-transformed myeloid cells. 284 75

The hemopoietic growth factor granulocyte-macrophage colony-stimulating factor, GM-CSF, specifically controls the production of granulocytes and macrophages. This report describes the binding of biologically-active 125I-labeled murine GM-CSF to a range of hemopoietic cells. Specific binding was restricted to murine cells and neither rat nor human bone marrow cells appeared to have surface receptors for 125I-labeled GM-CSF. 125I-Labeled GM-CSF only appeared to bind specifically to cells in the myelomonocytic lineage. The binding of 125I-labeled GM-CSF to both bone marrow cells and WEHI-3B(D+) was rapid (50% maximum binding was attained within 5 min at both 20 degrees C and 37 degrees C). Unlabeled GM-CSF was the only polypeptide hormone which completely inhibited the binding of 125I-labeled GM-CSF to bone marrow cells, however, multi-CSF (also called IL-3) and G-CSF partially reduced the binding of 125I-labeled GM-CSF to bone marrow cells. Interestingly, the binding of 125I-labeled GM-CSF to a myelomonocytic cell line, WEHI-3B(D+), was inhibited by unlabeled GM-CSF but not by multi-CSF or G-CSF. Scatchard analysis of the binding of 125I-labeled GM-CSF to WEHI-3B(D+) cells, bone marrow cells and peritoneal neutrophils indicated that there were two classes of binding sites: one of high affinity (Kd1 = 20 pM) and one of low affinity (Kd2 = 0.8-1.2 nM). Multi-CSF only inhibited the binding of 125I-labeled GM-CSF to the high affinity receptor on bone marrow cells: this inhibition appeared to be a result of down regulation or modification of the GM-CSF receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific binding of radioiodinated granulocyte-macrophage colony-stimulating factor to hemopoietic cells. 299 Sep 15

The hemopoietic growth and differentiation regulators, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the multipotential stimulating factor (multi-CSF) have been shown to have major effects on the effector function of mature macrophages. In this study we have examined the effect of recombinant GM-CSF and multi-CSF expressed transiently from recombinant vaccinia virus, or constitutively in GM-CSF transgenic mice on the development of cutaneous leishmaniasis, caused by Leishmania major in genetically susceptible or resistant mice. We observed no effect on the development of lesions when GM-CSF or multi-CSF were administered before infection, nor on the healing of lesions when they were administered after appearance of lesions. Although only some of the GM-CSF transgenic mice or their normal littermates developed lesions after infection with L. major, there was no difference between the groups in the rate of lesion development or in the size of lesions.
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PMID:GM-CSF produced by recombinant vaccinia virus or in GM-CSF transgenic mice has no effect in vivo on murine cutaneous leishmaniasis. 304 51

The x-irradiation biology of supportive stromal cells of the bone marrow microenvironment was investigated by using cloned permanent cell lines that were established from hematopoietically active murine long-term bone marrow cultures. X-irradiation survival curves were derived for each cell line at either 120 cGy/min or clinical low dose rate (LDR) (5 cGy/min) that is used in total body irradiation protocols prior to bone marrow transplantation. Four cell lines, MBA-1, MBA-13, 14F2.1, and D2XRII (Group I) demonstrated a significant increase in D0 at 5 cGy/min (280 cGy, 270 cGy, 210 cGy, and 240 cGy, respectively) compared to 120 cGy/min (215 cGy, 210 cGy, 157 cGy, and 210 cGy, respectively) (p less than 0.05). In contrast, three other clonal cell lines, +/+ #2 cl 4, S1d #3, and GPI alpha-1 (Group II) showed no significant dose rate dependent change in D0 at 5 cGy/min (164 cGy, 174 cGy, and 159 cGy, respectively) compared to 120 cGy/min (159 cGy, 167 cGy, and 143 cGy, respectively). Group I and II cell lines could not be distinguished by differences in synthesis of extracellular matrix proteins including laminin, collagen types I and IV, or histochemically detectable enzymes. Three Group I lines (MBA-1, MBA-13, and D2XRII) and one Group II line, Sld #3, showed decreased support capacity for cocultivated hematopoietic stem cells in vitro. All seven lines had detectable polyA+ mRNA for monocyte colony-stimulating factor (M-CSF) as detected by molecular hybridization; one had detectable levels of polyA+ mRNA for granulocyte-macrophage colony-stimulating factor (GM-CSF) (D2XRII); one, detectable levels of polyA+ mRNA for interleukin 1 (IL-1); and none of the seven had detectable polyA+ mRNA for granulocyte colony-stimulating factor (G-CSF) or IL-3 (multi-CSF). The data indicate that some cells of the hematopoietic microenvironment may not be selectively protected by clinical low dose rate irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Radiosensitivity of cloned permanent murine bone marrow stromal cell lines: nonuniform effect of low dose rate. 304 29

Interleukin-3 (IL-3) is a member of a family of growth factors, each of which supports the proliferation and development of hematopoietic precursors in culture. Although the biologic effects of the different hematopoietic growth factors have been well documented in different culture systems, it has only recently become possible to study the activities of these molecules in vivo. In comparison with the later acting hematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor, IL-3 elicited a delayed and relatively modest leukocytosis when continuously infused intravenously in primates. The IL-3 infusion, however, greatly potentiated the responsiveness of the animal to subsequent administration of a low dose of GM-CSF. These results suggest that IL-3 expands an early cell population in vivo that subsequently requires the action of a later acting factor such as GM-CSF to complete its development. Optimal stimulation of hematopoiesis may be achieved with combinations of hematopoietic growth factors.
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PMID:Human IL-3 and GM-CSF act synergistically in stimulating hematopoiesis in primates. 305 78

A group of cytokines characterized by a common set of target cells--namely, the pluripotential hemopoietic stem cells or their cellular derivatives--share similarities in the amino acid sequence at their N terminus or in the putative signal peptide immediately prior to the published N terminus. Murine P-cell-stimulating factor (PSF), murine and human interleukin 2 (IL-2), murine and human granulocyte-macrophage colony-stimulating factor (GM-CSF), human erythropoietin, and human interleukin 1 beta all share alanine as the N-terminal amino acid and have some similarities in the succeeding three or four amino acids. In the case of murine PSF and GM-CSF, the six N-terminal amino acids are readily cleaved from mature molecules and are lacking from the N-terminal amino acid sequences reported initially. A sixth cytokine, colony-stimulating factor 1, has an alanine followed by a similar pattern of five amino acids at the end of the putative signal peptide. GM-CSF and IL-2 have more extensive homology, about 25% of residues being identical in three regions that comprise about 70% of the molecules. Only minor similarities of uncertain significance were found among the complete amino acid sequences of the other cytokines. Although its evolutionary origin is uncertain, the homology around the N terminus may provide a structural marker for a group of cytokines active on the pluripotential hemopoietic stem cell and its derivatives.
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PMID:Structural homologies among the hemopoietins. 308 95

The effect of oxygen tensions in the physiological range as an environmental signal on the growth of in vitro murine hemopoietic progenitor cells and the production of hemopoietic growth factors (HGF) from macrophages was investigated. Early (BFU-E) and late (CFU-E) erythroid and granulocyte-macrophage (GM-CFC) progenitor cells were cultured in an atmosphere containing 2%, 3.5%, or 5% oxygen. For both the BFU-E and CFU-E populations, a gas phase containing 3.5% oxygen proved to be optimal, producing greater colony numbers than cultures incubated under 2% or 5% oxygen-tension conditions. For GM-CFC growth, 2% and 3.5% oxygen resulted in a greater stimulation than 5% oxygen. Macrophages derived from unseparated and unstimulated mouse bone marrow cells were cultured on hydrophobic Teflon foils under varying oxygen-tension conditions. The production of erythropoietin (epo), present in the culture supernatants, increased as the oxygen concentration increased from 2% to 3.5%, but then decreased as the oxygen concentration was increased further, from 3.5% to 5%. The presence of a factor demonstrating functional similarity with Interleukin-3 was produced optimally under 5% oxygen-tension conditions. The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) was not significantly affected by changing the oxygen-tension conditions. These results demonstrate that physiological oxygen tension plays an important role not only in the growth of hemopoietic progenitor cells, but also as a physiochemical signal that macrophages can sense and respond to in order to regulate the production of specific secretory products.
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PMID:A role for the macrophage in normal hemopoiesis. II. Effect of varying physiological oxygen tensions on the release of hemopoietic growth factors from bone-marrow-derived macrophages in vitro. 309 86


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