title: Borrelia burgdorferi, host-derived proteases, and the blood-brain barrier.
abstract: Neurological manifestations of Lyme disease in humans are attributed in part to penetration of the blood-brain barrier (BBB) and invasion of the central nervous system (CNS) by Borrelia burgdorferi. However, how the spirochetes cross the BBB remains an unresolved issue. We examined the traversal of B. burgdorferi across the human BBB and systemic endothelial cell barriers using in vitro model systems constructed of human brain microvascular endothelial cells (BMEC) and EA.hy 926, a human umbilical vein endothelial cell (HUVEC) line grown on Costar Transwell inserts. These studies showed that B. burgdorferi differentially crosses human BMEC and HUVEC and that the human BMEC form a barrier to traversal. During the transmigration by the spirochetes, it was found that the integrity of the endothelial cell monolayers was maintained, as assessed by transendothelial electrical resistance measurements at the end of the experimental period, and that B. burgdorferi appeared to bind human BMEC by their tips near or at cell borders, suggesting a paracellular route of transmigration. Importantly, traversal of B. burgdorferi across human BMEC induces the expression of plasminogen activators, plasminogen activator receptors, and matrix metalloproteinases. Thus, the fibrinolytic system linked by an activation cascade may lead to focal and transient degradation of tight junction proteins that allows B. burgdorferi to invade the CNS.
authors.affiliation: Department of Pediatrics, The Johns Hopkins University School of Medicine, Park Building, Room 256, 600 North Wolfe Street, Baltimore, MD 21287, USA. dgrab@jhmi.edu
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Grab
authors.forename: George
authors.initials: G
authors.lastname: Perides
authors.forename: J Stephen
authors.initials: JS
authors.lastname: Dumler
authors.forename: Kee Jun
authors.initials: KJ
authors.lastname: Kim
authors.forename: Jinho
authors.initials: J
authors.lastname: Park
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Kim
authors.forename: Olga
authors.initials: O
authors.lastname: Nikolskaia
authors.forename: Kyoung Seong
authors.initials: KS
authors.lastname: Choi
authors.forename: Monique F
authors.initials: MF
authors.lastname: Stins
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000382:microbiology; D025065:Borrelia burgdorferi / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008193:Lyme Disease / Q000378:metabolism* / Q000382:microbiology; D010447:Peptide Hydrolases / Q000378:metabolism*
chemical_list: D010447:Peptide Hydrolases