Source:http://linkedlifedata.com/resource/pubmed/id/21825068
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2011-9-22
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pubmed:abstractText |
Group B Streptococcus (GBS) is the most common bacterium causing neonatal meningitis, and neonatal GBS meningitis continues to be an important cause of mortality and morbidity. Here we provide the first direct evidence that host cytosolic phospholipase A?? (cPLA??) contributes to type III GBS invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier and penetration into the brain, the key step required for the development of GBS meningitis. This was shown by our demonstration that pharmacological inhibition and gene deletion of cPLA?? significantly decreased GBS invasion of the HBMEC monolayer and penetration into the brain. cPLA?? releases arachidonic acid from membrane phospholipids, and we showed that the contribution of cPLA?? to GBS invasion of HBMEC involved lipoxygenated metabolites of arachidonic acid, cysteinyl leukotrienes (LTs). In addition, type III GBS invasion of the HBMEC monolayer involves protein kinase C? (PKC?), as shown by time-dependent PKC? activation in response to GBS as well as decreased GBS invasion in HBMEC expressing dominant-negative PKC?. PKC? activation in response to GBS, however, was abolished by inhibition of cPLA?? and cysteinyl LTs, suggesting that cPLA?? and cysteinyl LTs contribute to type III GBS invasion of the HBMEC monolayer via PKC?. These findings demonstrate that specific host factors involving cPLA?? and cysteinyl LTs contribute to type III GBS penetration of the blood-brain barrier and their contribution involves PKC?.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotrienes,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2, Cytosolic,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/cysteinyl-leukotriene
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1098-5522
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
79
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4088-93
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pubmed:meshHeading |
pubmed-meshheading:21825068-Arachidonic Acid,
pubmed-meshheading:21825068-Blood-Brain Barrier,
pubmed-meshheading:21825068-Brain,
pubmed-meshheading:21825068-Cells, Cultured,
pubmed-meshheading:21825068-Cysteine,
pubmed-meshheading:21825068-Endothelial Cells,
pubmed-meshheading:21825068-Endothelium, Vascular,
pubmed-meshheading:21825068-Enzyme Activation,
pubmed-meshheading:21825068-Humans,
pubmed-meshheading:21825068-Leukotrienes,
pubmed-meshheading:21825068-Microcirculation,
pubmed-meshheading:21825068-Phospholipases A2, Cytosolic,
pubmed-meshheading:21825068-Protein Kinase C-alpha,
pubmed-meshheading:21825068-Streptococcus agalactiae
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pubmed:year |
2011
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pubmed:articleTitle |
Host cytosolic phospholipase A?? contributes to group B Streptococcus penetration of the blood-brain barrier.
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pubmed:affiliation |
Department of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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