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)

Products of the lipoxygenation of arachidonic acid have been shown to induce a variety of effects on cells of myeloid lineage. Colony-stimulating factor causes release of arachidonic acid from cell membranes, which then undergoes oxygenation via the cyclooxygenase and lipoxygenase pathways. Nordihydroguaiaretic acid (NDGA) and 3-amino-1-[m(trifluoromethyl)-phenyl]-2-pyrazoline (BW 755C), compounds that inhibit both the cyclooxygenase and lipoxygenase pathways, cause dose-dependent inhibition of CSF-induced human granulocyte-monocyte colony formation in vitro, with complete inhibition at 20 and 50 microM, respectively. Indomethacin, which inhibits cyclooxygenase but not lipoxygenase, has no effect on colony growth at 50 microM, which is well in excess of the dose needed for complete inhibition of cyclooxygenase. Leukotrienes (LTs) C4 and D4 (5-100 ng/ml) reverse NDGA inhibition of colony growth. At similar concentrations, neither leukotriene B4 or 5-HETE caused reversal of NDGA inhibition. These results support a role for LTC4 and LTD4 as essential intermediates in CSF-stimulated myeloid colony formation.
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PMID:Evidence for the role of leukotrienes C4 and D4 as essential intermediates in CSF-stimulated human myeloid colony formation. 309 87

Although lipid bodies, inducible cytoplasmic inclusions active in arachidonic acid metabolism, are abundant in activated leukocytes, including eosinophils, mechanisms for eosinophil lipid body formation are not certain. Eosinophils from hypereosinophilic syndrome (HES) donors contained about twice (approximately 18/cell) as many lipid bodies as eosinophils froin normal donors (approximately 10/cell). By immunocytochemistry both 5- and 15-lipoxygenases were localized at lipid bodies in HES eosinophils. Platelet-activating factor (PAF) induced rapid, receptor-mediated increases in lipid bodies in normal and HES eosinophils. Protein kinase C (PKC) inhibitors, chelerythrine and calphostin C, inhibited PAF-induced lipid body formation partially in normal and HES eosinophils. In HES, but not normal, eosinophils, PAF-induced lipid body formation was completely blocked by two tyrosine kinase inhibitors, herbimycin A and genistein, which were not acting on 5-lipoxygenase because they also blocked 5-HETE-induced lipid body formation in HES, and not normal, eosinophils. After 24 h culture with eosinophil growth factor cytokines [interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM-CSF alone but not IL-5 or IL-3 alone], normal eosinophils were induced to exhibit an HES-like phenotype, including increased lipid body numbers and tyrosine kinase-dependent signaling for PAF-induced lipid body formation. Thus, signal transduction mechanisms involved in PAF-induced lipid body formation in eosinophils can be differentially recruited. Tyrosine kinase-dependent signaling is not involved in normal eosinophils, but is active in HES eosinophils and in normal eosinophils cultured with GM-CSF. PKC- and tyrosine kinase-dependent pathways are involved in the formation of eosinophil lipid bodies, which may facilitate enhanced synthesis of lipoxygenase-derived eicosanoids.
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PMID:Pathways for eosinophil lipid body induction: differing signal transduction in cells from normal and hypereosinophilic subjects. 976 38