Browsing by Author "Nikolskaia, O.V."
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Item Anaplasma phagocytophilum-Borrelia burgdorferi coinfection enhances chemokine, cytokine, and matrix metalloprotease expression by human brain microvascular endothelial cells(Clinical and Vaccine Immunology, 2007-12) Grab, D.J.; Nyarko, E.; Barat, N.C.; Nikolskaia, O.V.; Dumler, J.S.Borrelia burgdorferi and Anaplasma phagocytophilum coinfect and are transmitted by Ixodes species ticks. Clinical indicators suggest that A. phagocytophilum coinfection contributes to the severity, dissemination, and, possibly, sequelae of Lyme disease. Previous in vitro studies showed that spirochete penetration through human brain microvascular endothelial cells of the blood-brain barrier is facilitated by endothelial cell-derived matrix metalloproteases (MMPs). A. phagocytophilum-inkcted neutrophils continuously release MMPs and other vasoactive biomediators. We examined B. burgdorferi infection of brain microvascular barriers during A. phagocytophilum coinfection and showed that coinfection enhanced reductions in transendothelial electrical resistance and enhanced or synergistically increased production of MMPs (MMP-1, -3, -7, -8, and -9), cytokines (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha), and chemokines (IL-8 and macrophage inflammatory protein 1α) known to affect vascular permeability and inflammatory responses. Copyright © 2007, American Society for Microbiology. All Rights Reserved.Item Human brain microvascular endothelial cell traversal by Borrelia burgdorferi requires calcium signaling(Clinical Microbiology and Infection, 2009-05) Grab, D.J.; Nyarko, E.; Nikolskaia, O.V.; Kim, Y.V.; Dumler, J.S.Neurological manifestations of Lyme disease (or neuroborreliosis) occur variably and while it is clear thatBorrelia burgdorferican invadethe nervous system, how it does so is not well understood. Pathogen penetration through the blood brain barrier (BBB) is often influ-enced by calcium signaling in the endothelial cells triggered by extracellular host-pathogen interactions. We examined the traversal ofB. burgdorferiacross the human BBB usingin vitromodel systems constructed of human brain microvascular endothelial cells (HBMEC)grown on Costar TranswellÔinserts. Pretreatment of the cell monolayers with BAPTA-AM (an intracellular calcium chelator) or phos-pholipase C (PLC) inhibitor U73122 inhibitedB. burgdorferitransmigration. 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) afterpretreatment with the PLC-binhibitor 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.