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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1998-4-15
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pubmed:abstractText |
Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. We studied the effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae, an important gram-negative bacillary pulmonary pathogen. Using a highly reproducible murine model, we here show the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Binding of 125I-G-CSF to K pneumoniae was displaced by an excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1alpha, did not compete with G-CSF binding to the bacteria. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
|
pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
91
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2525-35
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9516154-Animals,
pubmed-meshheading:9516154-Female,
pubmed-meshheading:9516154-Granulocyte Colony-Stimulating Factor,
pubmed-meshheading:9516154-Klebsiella Infections,
pubmed-meshheading:9516154-Klebsiella pneumoniae,
pubmed-meshheading:9516154-Lung,
pubmed-meshheading:9516154-Mice,
pubmed-meshheading:9516154-Mice, Inbred BALB C,
pubmed-meshheading:9516154-Pneumonia, Bacterial,
pubmed-meshheading:9516154-Polysaccharides, Bacterial,
pubmed-meshheading:9516154-Survival Analysis
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pubmed:year |
1998
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pubmed:articleTitle |
Granulocyte colony-stimulating factor worsens the outcome of experimental Klebsiella pneumoniae pneumonia through direct interaction with the bacteria.
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pubmed:affiliation |
Department of Hematology and Oncology, Virchow-Klinikum, Humboldt-University, Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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