title: Arachidonic acid metabolism regulates Escherichia coli penetration of the blood-brain barrier.
abstract: Escherichia coli K1 meningitis occurs following penetration of the blood-brain barrier, but the underlying mechanisms involved in E. coli penetration of the blood-brain barrier remain incompletely understood. We have previously shown that host cytosolic phospholipase A(2)α (cPLA(2)α) contributes to E. coli invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier, but the underlying mechanisms remain unclear. cPLA(2)α selectively liberates arachidonic acid from membrane phospholipids. Here, we provide the first direct evidence that host 5-lipoxygenase and lipoxygenase products of arachidonic acid, cysteinyl leukotrienes (LTs), contribute to E. coli K1 invasion of HBMEC and penetration into the brain, and their contributions involve protein kinase C alpha (PKCα). These findings demonstrate that arachidonic acid metabolism regulates E. coli penetration of the blood-brain barrier, and studies are needed to further elucidate the mechanisms involved with metabolic products of arachidonic acid for their contribution to E. coli invasion of the blood-brain barrier.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Longkun
authors.initials: L
authors.lastname: Zhu
authors.forename: Ravi
authors.initials: R
authors.lastname: Maruvada
authors.forename: Adam
authors.initials: A
authors.lastname: Sapirstein
authors.forename: Kafait U
authors.initials: KU
authors.lastname: Malik
authors.forename: Marc
authors.initials: M
authors.lastname: Peters-Golden
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000382:microbiology / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D042783:Endothelial Cells / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology*; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051571:Protein Kinase C-alpha / Q000378:metabolism
chemical_list: D015289:Leukotrienes; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D051571:Protein Kinase C-alpha; D054513:Group IV Phospholipases A2