Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2011-9-22
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?.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1098-5522
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4088-93
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Host cytosolic phospholipase A?? contributes to group B Streptococcus penetration of the blood-brain barrier.
pubmed:affiliation
Department of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural