title: Involvement of IbeA in meningitic Escherichia coli K1-induced polymorphonuclear leukocyte transmigration across brain endothelial cells.
abstract: Transmigration of neutrophil [polymorphonuclear neutrophil (PMN)] across the blood-brain barrier (BBB) is a critical event in the pathogenesis of bacterial meningitis. We have shown that IbeA is able to induce meningitic Escherichia coli invasion of brain microvascular endothelial cells (BMECs), which constitutes the BBB. In this report, we provide evidence that IbeA and its receptor, vimentin, play a key role in E. coli-induced PMN transmigration across BMEC. In vitro and in vivo studies indicated that the ibeA-deletion mutant ZD1 was significantly less active in stimulating PMN transmigration than the parent strain E44. ZD1 was fully complemented by the ibeA gene and its product. E. coli-induced PMN transmigration was markedly inhibited by withaferin A, a dual inhibitor of vimentin and proteasome. These cellular effects were significantly stimulated and blocked by overexpression of vimentin and its head domain deletion mutant in human BMEC, respectively. Our studies further demonstrated that IbeA-induced PMN migration was blocked by bortezomib, a proteasomal inhibitor and correlated with upregulation of endothelial ICAM-1 and CD44 expression through proteasomal regulation of NFκB activity. Taken together, our data suggested that IbeA and vimentin contribute to E. coli K1-stimulated PMN transendothelial migration that is correlated with upregulation of adhesion molecule expression at the BBB.
authors.affiliation: Saban Research Institute of Childrens Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, CA 90027, USA.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Che
authors.forename: Feng
authors.initials: F
authors.lastname: Chi
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Jong
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wu
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.forename: Sheng-He
authors.initials: SH
authors.lastname: Huang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000378:metabolism*; D020814:Meningitis, Escherichia coli / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D014746:Vimentin / Q000276:immunology / Q000378:metabolism
chemical_list: C096350:CusC protein, E coli; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D014746:Vimentin