Differential role of cytosolic phospholipase A2 in the invasion of brain microvascular endothelial cells by Escherichia coli and Listeria monocytogenes.
Invasion of brain microvascular endothelial cells (BMECs) is a key step in the pathogenesis of meningitis due to Escherichia coli and Listeria monocytogenes. Although host cell actin cytoskeletal rearrangements are essential in BMEC invasion by E. coli K1 and L. monocytogenes, the underlying signaling mechanisms remain unclear. This study demonstrates that host cell cytosolic phospholipase A2 (cPLA2) contributes to E. coli K1 invasion of BMECs but not to L. monocytogenes invasion of BMECs. This difference was observed with 4-bromophenacyl bromide, a nonselective PLA2 inhibitor, and arachidonyl trifluoromethyl ketone, a selective cPLA2 inhibitor, and was confirmed with BMEC derived from cPLA2 knockout mice. Activation of cPLA2 leads to generation of intracellular arachidonic acid, which is metabolized via cyclooxygenase (COX) and lipo-oxygenase (LOX) pathways into eicosanoids. COX and LOX inhibitors also significantly inhibit E. coli K1 invasion of BMECs.
Das
A
A
Division of Infectious Diseases, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA. adas@chla.usc.edu
Asatryan
L
L
Reddy
M A
MA
Wass
C A
CA
Stins
M F
MF
Joshi
S
S
Bonventre
J V
JV
Kim
K S
KS
D000470:Alkaloids / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D044182:Benzylisoquinolines; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D003600:Cytosol / Q000201:enzymology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000382:microbiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D009637:Masoprocol / Q000494:pharmacology; D008833:Microcirculation / Q000201:enzymology / Q000382:microbiology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D015398:Signal Transduction
D000470:Alkaloids; D001095:Arachidonic Acids; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; C081565:arachidonyltrifluoromethane; C009438:tetrandrine; D009637:Masoprocol; D010741:Phospholipases A; D054467:Phospholipases A2; D007213:Indomethacin