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.