This Article Full Text Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grab, D. J. Articles by Kim, K. S. Search for Related Content PubMed PubMed Citation Articles by Grab, D. J. Articles by Kim, K. S.

Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Department of Pediatrics,¹ Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland,³ New England Medical Center, Boston Massachusetts²

Received 14 April 2004/ Returned for modification 22 May 2004/ Accepted 13 October 2004

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.

Editor: W. A. Petri, Jr.

This article has been cited by other articles:

• Livengood, J. A., Schmit, V. L., Gilmore, R. D. Jr. (2008). Global Transcriptome Analysis of Borrelia burgdorferi during Association with Human Neuroglial Cells. Infect. Immun. 76: 298-307 [Abstract] [Full Text]  
• Grab, D. J., Nyarko, E., Barat, N. C., Nikolskaia, O. V., Dumler, J. S. (2007). Anaplasma phagocytophilum-Borrelia burgdorferi Coinfection Enhances Chemokine, Cytokine, and Matrix Metalloprotease Expression by Human Brain Microvascular Endothelial Cells. CVI 14: 1420-1424 [Abstract] [Full Text]  
• Vojdani, A., Hebroni, F., Raphael, Y., Erde, J., Raxlen, B. (2007). Novel Diagnosis of Lyme Disease: Potential for CAM Intervention. Evid Based Complement Alternat Med 0: nem138v1-nem138 [Abstract] [Full Text]  
• Rossmann, E., Kraiczy, P., Herzberger, P., Skerka, C., Kirschfink, M., Simon, M. M., Zipfel, P. F., Wallich, R. (2007). Dual Binding Specificity of a Borrelia hermsii-Associated Complement Regulator-Acquiring Surface Protein for Factor H and Plasminogen Discloses a Putative Virulence Factor of Relapsing Fever Spirochetes. J. Immunol. 178: 7292-7301 [Abstract] [Full Text]  
• Sethi, N., Sondey, M., Bai, Y., Kim, K. S., Cadavid, D. (2006). Interaction of a Neurotropic Strain of Borrelia turicatae with the Cerebral Microcirculation System. Infect. Immun. 74: 6408-6418 [Abstract] [Full Text]