Arachidonic acid metabolism regulates Escherichia coli penetration of the blood-brain barrier

Longkun Zhu, Ravi Maruvada, Adam Sapirstein, Kafait U. Malik, Marc Peters-Golden, Kwang Sik Kim

Research output: Contribution to journalArticlepeer-review

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 A2α (cPLA2α) contributes to E. coli invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier, but the underlying mechanisms remain unclear. cPLA2α 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.

Original languageEnglish (US)
Pages (from-to)4302-4310
Number of pages9
JournalInfection and immunity
Volume78
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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