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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2011-3-25
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pubmed:abstractText |
Hemorrhagic meningitis is a fatal complication of anthrax, but its pathogenesis remains poorly understood. The present study examined the role of B. anthracis-secreted metalloprotease InhA on monolayer integrity and permeability of human brain microvasculature endothelial cells (HBMECs) which constitute the blood-brain barrier (BBB). Treatment of HBMECs with purified InhA resulted in a time-dependent decrease in trans-endothelial electrical resistance (TEER) accompanied by zonula occluden-1 (ZO-1) degradation. An InhA-expressing B. subtilis exhibited increased permeability of HBMECs, which did not occur with the isogenic inhA deletion mutant (?inhA) of B. anthracis, compared with the corresponding wild-type strain. Mice intravenously administered with purified InhA or nanoparticles-conjugated to InhA demonstrated a time-dependent Evans Blue dye extravasation, leptomeningeal thickening, leukocyte infiltration, and brain parenchymal distribution of InhA indicating BBB leakage and cerebral hemorrhage. Mice challenged with vegetative bacteria of the ?inhA strain of B. anthracis exhibited a significant decrease in leptomeningeal thickening compared to the wildtype strain. Cumulatively, these findings indicate that InhA contributes to BBB disruption associated with anthrax meningitis through proteolytic attack on the endothelial tight junctional protein zonula occluden (ZO)-1.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21437287-11353060,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/21437287-9746589
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1932-6203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e17921
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pubmed:dateRevised |
2011-7-27
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pubmed:meshHeading |
pubmed-meshheading:21437287-Animals,
pubmed-meshheading:21437287-Anthrax,
pubmed-meshheading:21437287-Bacillus anthracis,
pubmed-meshheading:21437287-Bacterial Proteins,
pubmed-meshheading:21437287-Blood-Brain Barrier,
pubmed-meshheading:21437287-Blotting, Western,
pubmed-meshheading:21437287-Cerebral Hemorrhage,
pubmed-meshheading:21437287-Cytoplasm,
pubmed-meshheading:21437287-Electric Impedance,
pubmed-meshheading:21437287-Endothelial Cells,
pubmed-meshheading:21437287-Female,
pubmed-meshheading:21437287-Humans,
pubmed-meshheading:21437287-Membrane Proteins,
pubmed-meshheading:21437287-Metalloproteases,
pubmed-meshheading:21437287-Mice,
pubmed-meshheading:21437287-Mutant Proteins,
pubmed-meshheading:21437287-Nanospheres,
pubmed-meshheading:21437287-Permeability,
pubmed-meshheading:21437287-Phosphoproteins
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pubmed:year |
2011
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pubmed:articleTitle |
Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages.
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pubmed:affiliation |
National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia, United States of America.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
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