Journal
CLINICAL MICROBIOLOGY AND INFECTION
Volume 15, Issue 5, Pages 422-426Publisher
ELSEVIER SCI LTD
DOI: 10.1111/j.1469-0691.2009.02869.x
Keywords
Blood-brain barrier; Borrelia burgdorferi; calcium signaling; endothelial cells; Lyme disease
Categories
Funding
- National Institutes of Health [R21NS050711, R01AI41213]
- American Heart Association [0435177N]
- National Research Fund for Tick-Borne Diseases, Inc.
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Neurological manifestations of Lyme disease (or neuroborreliosis) occur variably and while it is clear that Borrelia burgdorferi can invade the nervous system, how it does so is not well understood. Pathogen penetration through the blood brain barrier (BBB) is often influenced by calcium signaling in the endothelial cells triggered by extracellular host-pathogen interactions. We examined the traversal of B. burgdorferi across the human BBB using in vitro model systems constructed of human brain microvascular endothelial cells (HBMEC) grown on Costar Transwell (TM) inserts. Pretreatment of the cell monolayers with BAPTA-AM (an intracellular calcium chelator) or phospholipase C (PLC) inhibitor U73122 inhibited B. burgdorferi transmigration. By 5 h, BAPTA-AM significantly inhibited (82-99%; p < 0.017) spirochete traversal of HBMEC compared to DMSO controls. Spirochete traversal was almost totally blocked (>= 99%; p < 0.017) after pretreatment with the PLC-beta inhibitor U73122 as a result of barrier tightening based on electric cell-substrate impedance sensing (ECIS). The data suggest a role for calcium signaling in CNS spirochete invasion through endothelial cell barriers.
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