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Von-Willebrand Factor Influences Blood Brain Barrier Permeability and Brain Inflammation in Experimental Allergic Encephalomyelitis
Journal article   Open access   Peer reviewed

Von-Willebrand Factor Influences Blood Brain Barrier Permeability and Brain Inflammation in Experimental Allergic Encephalomyelitis

Rajkumar Noubade, Roxana del Rio, Benjamin McElvany, James F Zachary, Jason M Millward, Denisa D Wagner, Halina Offner, Elizabeth P Blankenhorn and Cory Teuscher
The American journal of pathology, v 173(3), pp 892-900
Sep 2008
PMID: 18688020
url
https://doi.org/10.2353/ajpath.2008.080001View
Published, Version of Record (VoR) Open

Abstract

Regular
Weibel-Palade bodies within endothelial cells are secretory granules known to release von Willebrand Factor (VWF), P-selectin, chemokines, and other stored molecules following histamine exposure. Mice with a disrupted VWF gene (VWFKO) have endothelial cells that are deficient in Weibel-Palade bodies. These mice were used to evaluate the role of VWF and/or Weibel-Palade bodies in Bordetella pertussis toxin-induced hypersensitivity to histamine, a subphenotype of experimental allergic encephalomyelitis, the principal autoimmune model of multiple sclerosis. No significant differences in susceptibility to histamine between wild-type and VWFKO mice were detected after 3 days; however, histamine sensitivity persisted significantly longer in VWFKO mice. Correspondingly, encephalomyelitis onset was earlier, disease was more severe, and blood brain barrier (BBB) permeability was significantly increased in VWFKO mice, as compared with wild-type mice. Moreover, inflammation was selectively increased in the brains, but not spinal cords, of VWFKO mice as compared with wild-type mice. Early increases in BBB permeability in VWFKO mice were not due to increased encephalitogenic T-cell activity since BBB permeability did not differ in adjuvant-treated VWFKO mice as compared with littermates immunized with encephalitogenic peptide plus adjuvant. Taken together, these data indicate that VWF and/or Weibel-Palade bodies negatively regulate BBB permeability changes and autoimmune inflammatory lesion formation within the brain elicited by peripheral inflammatory stimuli.

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Web of Science research areas
Pathology
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