TY - JOUR
T1 - Host cytosolic phospholipase A2α contributes to group B streptococcus penetration of the blood-brain barrier
AU - Maruvada, Ravi
AU - Zhu, Longkun
AU - Pearce, Donna
AU - Sapirstein, Adam
AU - Kim, Kwang Sik
PY - 2011/10
Y1 - 2011/10
N2 - 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 A2α (cPLA2α) 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 cPLA2α significantly decreased GBS invasion of the HBMEC monolayer and penetration into the brain. cPLA2α releases arachidonic acid from membrane phospholipids, and we showed that the contribution of cPLA2α 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 Cα (PKCα), as shown by time-dependent PKCα activation in response to GBS as well as decreased GBS invasion in HBMEC expressing dominant-negative PKCα. PKCα activation in response to GBS, however, was abolished by inhibition of cPLA2α and cysteinyl LTs, suggesting that cPLA2α and cysteinyl LTs contribute to type III GBS invasion of the HBMEC monolayer via PKCα. These findings demonstrate that specific host factors involving cPLA2α and cysteinyl LTs contribute to type III GBS penetration of the blood-brain barrier and their contribution involves PKC.
AB - 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 A2α (cPLA2α) 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 cPLA2α significantly decreased GBS invasion of the HBMEC monolayer and penetration into the brain. cPLA2α releases arachidonic acid from membrane phospholipids, and we showed that the contribution of cPLA2α 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 Cα (PKCα), as shown by time-dependent PKCα activation in response to GBS as well as decreased GBS invasion in HBMEC expressing dominant-negative PKCα. PKCα activation in response to GBS, however, was abolished by inhibition of cPLA2α and cysteinyl LTs, suggesting that cPLA2α and cysteinyl LTs contribute to type III GBS invasion of the HBMEC monolayer via PKCα. These findings demonstrate that specific host factors involving cPLA2α and cysteinyl LTs contribute to type III GBS penetration of the blood-brain barrier and their contribution involves PKC.
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U2 - 10.1128/IAI.05506-11
DO - 10.1128/IAI.05506-11
M3 - Article
C2 - 21825068
AN - SCOPUS:80755180516
SN - 0019-9567
VL - 79
SP - 4088
EP - 4093
JO - Infection and immunity
JF - Infection and immunity
IS - 10
ER -