Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

A naturally occurring inducer of terminal differentiation in a murine myelomonocytic leukemia cell line (WEHI-3B) was purified to apparent homogeneity from medium conditioned by lungs from mice injected with bacterial endotoxin. The factor was purified over 400,000-fold by sequential fractionation using salting out chromatography, chromatography on phenyl-Sepharose, gel filtration on Bio-Gel P-60 in 1 M acetic acid, reverse-phase high performance liquid chromatography on a phenyl-silica column, and high performance liquid chromatography on a gel filtration column. During the first two steps, the differentiation-inducing factor was separated completely from a known proliferative regulator for normal myeloid cells, granulocyte-macrophage colony-stimulating factor, but it co-purified through all remaining steps with a distinct granulocyte-specific colony-stimulating factor. The purified factor showed a single protein band of Mr = 24,000-25,000 on sodium dodecyl sulfate-polyacrylamide gels coincident with both differentiation-inducing and granulocyte colony-stimulating activity. The granulocyte-specific colony-stimulating factor was active on WEHI-3B cells and normal granulocytic progenitor cells in vitro at the same half-maximally active concentration of 3 X 10(-12) M.
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PMID:Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. 619 Aug 15

Preincubation of human neutrophils with the human cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) results in an increase in the amount of alpha-subunit of Gi2 (Gi alpha 2) associated with the plasma membrane and a corresponding decrease in the amount associated with the granule fractions. Similar results are obtained with interleukin-8. GM-CSF has no effect on the distribution of Gi alpha 3. The effect of GM-CSF on Gi alpha 2 is time-dependent, and, although a significant effect can be observed after incubation for 5 min with GM-CSF, the enhancement increases with increasing time. Genistein, a protein tyrosine kinase inhibitor, and 1,2-bis-(O-aminophenoxyl)ethane-NNN'N'-tetra-acetic acid (BAPTA), an intracellular Ca2+ chelator, decrease the stimulatory effect of GM-CSF. On the other hand, the protein-synthesis inhibitor cycloheximide does not affect the action of GM-CSF. Also, although preincubation of human neutrophils with GM-CSF increases the levels of Gi alpha 2 in the plasma membrane it does not alter the total amount of cellular Gi alpha 2. In addition, the level of Gi alpha 2 mRNA, unlike that of the proto-oncogene c-fos, is not increased in cells treated with GM-CSF. This indicates that the observed increase in the amount of Gi alpha 2 associated with the plasma membrane is not due to the synthesis of new Gi alpha 2. These data provide insight into the mechanism by which GM-CSF may prime human neutrophils for increased responsiveness to subsequent stimulation by G-protein-dependent agonists.
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PMID:Up-regulation of the amount of Gi alpha 2 associated with the plasma membrane in human neutrophils stimulated by granulocyte-macrophage colony-stimulating factor. 850 45

Essentially pure (>95%) cultures of microglia were established from neopallia of newborn rats and used for whole-cell patch-clamp recording of electrophysiological properties and for proliferation studies. Two types of cultures were examined: 1) "Primary" cultures were grown in culture medium with serum and used within 3 weeks of isolation; 2) and "Colony-stimulating factor (CSF)-1-stimulated" cultures were derived from 3-week-old "primary" cultures by passaging and culturing them for several weeks longer in the presence of conditioned medium enriched in CSF-1. Microglia in the "primary" cultures expressed: 1) an inwardly rectifying K+ current (Kir) that was inhibited by Ba2+; 2) an outwardly rectifying K+ current (Kv) with many similarities to the cloned Kv1.3 channel of lymphocytes, including block by nanomolar concentrations of charybdotoxin (ChTX) and margatoxin (MgTX); and 3) an outwardly rectifying anion current with time- and voltage-independent gating. The anion current is activated reversibly under cell swelling conditions, i.e., after exposure to a hypo-osmotic bathing medium. The anion channels are highly permeable to Cl-, measurably permeable to gluconate (P(gluconate)/ PCl = 0.34), and blocked by flufenamic acid, 4-nitro-2-(3-phenylpropylamino)- benzoic acid (NPPB), and 6, 7-dichloro-2-cyclopentyl-2, 3-dihydro-2-methyl-1-oxo-1H-inden-5-yl (oxy) acetic acid (IAA-94). Microglia in the "CSF-1-stimulated" cultures expressed Kir and Cl- current, but not Kv current. Proliferation in the latter type of cultures could be slowed by omission of the CSF-1 enriched supernatant for 2 days and stimulated by adding back the conditioned medium. This "CSF-1-stimulated" proliferation was inhibited by Ba2+ (Kir blocker), and the Cl(-)-channel blockers flufenamic acid, NPPB, and IAA-94, whereas the Kv blockers ChTX and MgTX had no effect. Thus, Kir and Cl- channels appear to be necessary for "CSF-1-stimulated" proliferation of rat microglia, and there is no evidence that even a transient activation of Kv is necessary.
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PMID:Properties of K+ and Cl- channels and their involvement in proliferation of rat microglial cells. 884 Jan 64

We have prepared a new formulation for mucosal delivery of GM-CSF or PEGylated GM-CSF based on a chitosan carrier plus added glycerol to control the rate of release of the protein. Thin dry films comprised of various weight ratios of chitosan to glycerol and containing either granulocyte-macrophage colony-stimulating factor (GM-CSF) or PEGylated GM-CSF, PEG-(GM-CSF), were prepared. The amount of GM-CSF or PEG-(GM-CSF) released from the chitosan/glycerol films was determined using size exclusion high performance liquid chromatography (HPLC-SEC). The amount of PEG-(GM-CSF) released from the films decreased with an increase in the amount of glycerol present in the film. In parallel with this, films with higher glycerol content exhibited a lower degree of equilibrium swelling when immersed in release media. pH measurements of the release media and analysis of the dried films by Fourier-transform infrared spectroscopy (FTIR) suggested that the amount of residual acetic acid in the dry films decreased as the glycerol content increased. This indicates that glycerol may act by displacing and releasing bound acetic acid from the chitosan molecules, resulting in chitosan--glycerol hydrogen bond formation as the film dries. Further, it was found that the release rate and the amount of PEG-(GM-CSF) released decreased with increasing molecular weight of the conjugated PEG. This effect was not observed with films containing physical mixtures of PEG and GM-CSF. The decrease in the fraction of PEG-(GM-CSF) released with increasing PEG molecular weight is believed to be due to the increased steric hindrance of the PEGylated protein molecule during its diffusion out of the swollen chitosan/glycerol film.
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PMID:Release of PEGylated granulocyte-macrophage colony-stimulating factor from chitosan/glycerol films. 1138 83