Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eosinophilic and neutrophilic granulocytes represent major effector cells in the inflammatory response. Whereas neutrophils are predominantly involved in bacterial infections, eosinophils are of essential importance in the allergic inflammation. Surface markers have been used to distinguish neutrophils (CD16+) from eosinophils (CD16-) and might indicate different functional properties of these cells. In this study, expression and functional activity of CD52 on human eosinophils and neutrophils was investigated in nonatopic healthy donors and from patients with hypereosinophilia. Flow cytometric analysis using different anti-CD52 monoclonal antibodies (MoAbs) (mouse IgG3, humanized IgG1, and rat IgM) showed significant and homogeneous expression of CD52 on human eosinophils, but not on neutrophils. In addition, reverse transcription-polymerase chain reaction and Northern blot analysis showed that CD52 mRNA was constitutively expressed in eosinophils but not in neutrophils. Furthermore, expression of CD52 could be diminished in a dose-dependent manner by preincubation of eosinophils with phosphatidylinositol-specific phospholipase C, suggesting that CD52 on eosinophils is anchored to the membrane through a glycosylphosphatidylinositol (GPI) molecule. Whereas the phorbolester phorbol myristate acetate was able to downregulate the expression of CD52 on eosinophils in a dose-dependent manner, different eosinophil activating cytokines and chemotaxins had no effect. Cross-linking of CD52 by mouse anti-CD52 MoAb (IgG3) and humanized anti-CD52 MoAb (IgG1) with goat antimouse antibody and mouse antihuman antibody, respectively, dose-dependently resulted in an inhibition of reactive oxygen species production of eosinophils after stimulation with C5a, platelet-activating factor, and granulocyte-macrophage colony-stimulating factor. In summary, this study shows that the GPI-anchored antigen CD52 is not only a useful marker to distinguish eosinophils from neutrophils. The data point out a novel role of the CD52 antigen on human eosinophils that might be of clinical relevance, because cross-linking of this molecule will stop the destructive power of human eosinophils in the inflammatory tissue.
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PMID:Surface and mRNA expression of the CD52 antigen by human eosinophils but not by neutrophils. 897 62

The interaction of Listeria monocytogenes with endothelial cells represents a crucial step in the pathogenesis of listeriosis. Incubation of human umbilical vein endothelial cells (HUVEC) with wild-type L. monocytogenes (EGD) provoked immediate strong NO synthesis, attributable to listerial presentation of listeriolysin O (LLO), as the NO release was missed upon employment of a deletion mutant for LLO (EGD hly mutant) and was reproduced by purified LLO. Studies of conditions lacking extracellular Ca(2+) suggested LLO-elicited Ca(2+) flux as the underlying mechanism. In addition, HUVEC incubation with EGD turned out to be a potent stimulus for sustained (>12-h) upregulation of proinflammatory cytokine generation (interleukin 6 [IL-6], IL-8, and granulocyte-macrophage colony-stimulating factor). Use of deletion mutants for LLO (EGD hly mutant), listerial phosphatidylinositol-specific phospholipase C (EGD plcA mutant), broad-spectrum phospholipase C (EGD plcB mutant) and internalin B (EGD inlB mutant), as well as purified LLO, identified LLO as largely responsible for the cytokine response. Endothelial cells responded with diacylglycerole and ceramide generation as well as nuclear translocation of NF-kappa B to the stimulation with the LLO-producing strains EGD and Listeria innocua. The endothelial PC-phospholipase C inhibitor tricyclodecan-9-yl-xanthogenate as well as two independent inhibitors of NF-kappa B activation, pyrolidine dithiocarbamate and caffeic acid phenethyl ester, suppressed both the NF-kappa B translocation and the upregulation of cytokine synthesis. We conclude that L. monocytogenes is a potent stimulus of NO release and sustained upregulation of proinflammatory cytokine synthesis in human endothelial cells, both events being largely attributable to LLO presentation. LLO-induced transmembrane Ca(2+) flux as well as a sequence of endothelial phospholipase activation and the appearance of diacylglycerole, ceramide, and NF-kappa B are suggested as underlying host signaling events. These endothelial responses to L. monocytogenes may well contribute to the pathogenic sequelae in severe listerial infection and sepsis.
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PMID:Human endothelial cell activation and mediator release in response to Listeria monocytogenes virulence factors. 1115 83

There are a variety of dermal and mucosal lesions involving keratinocytes. We examined here the signal transduction of lipopolysaccharide (LPS) in oral keratinocytes. Oral keratinocytes did not express CD14, but expression of CD58 and CD59 was observed by flow cytometry and reverse transcription-PCR. The binding between LPS and keratinocytes was strongly inhibited by pretreatment of keratinocytes with anti-CD59 monoclonal antibody (mAb) or phosphatidylinositol-specific phospholipase C (PI-PLC) but was not inhibited by anti-CD14 or anti-CD58 mAb. In LPS-treated keratinocytes, nuclear translocation of nuclear factor-kappa B (NF-kappaB) was induced and generation of granulocyte-macrophage colony-stimulating factor, interleukin-6 and tumour necrosis factor-alpha was enhanced. These upregulations in nuclear translocation of NF-kappaB and cytokine generation were not suppressed by anti-CD14 mAb or anti-CD58 mAb but were suppressed by anti-CD59 mAb and PI-PLC. Moreover, the transfection of CD59 antisense oligonucleotide into keratinocytes markedly suppressed LPS-induced nuclear translocation of NF-kappaB and cytokine generation. These results indicate that, through CD59, the LPS signal is transduced into the nucleus via NF-kappaB activation inducing cytokine generation, which may be involved in dermal and mucosal inflammatory diseases.
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PMID:Lipopolysaccharide signal transduction in oral keratinocytes--involvement of CD59 but not CD14. 1283 11