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, Cory Teuscher

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)892-900
Number of pages9
JournalAmerican Journal of Pathology
Volume173
Issue number3
DOIs
StatePublished - Sep 2008
Externally publishedYes

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Autoimmune Experimental Encephalomyelitis
von Willebrand Factor
Encephalitis
Blood-Brain Barrier
Permeability
Weibel-Palade Bodies
Histamine
Endothelial Cells
Encephalomyelitis
Bordetella pertussis
P-Selectin
Pertussis Toxin
Secretory Vesicles
Brain
Chemokines
Multiple Sclerosis
Spinal Cord
Hypersensitivity
Inflammation
T-Lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Von-Willebrand factor influences blood brain barrier permeability and brain inflammation in experimental allergic encephalomyelitis. / Noubade, Rajkumar; Del Rio, Roxana; McElvany, Benjamin; Zachary, James F.; Millward, Jason M.; Wagner, Denisa D.; Offner, Halina; Blankenhorn, Elizabeth P.; Teuscher, Cory.

In: American Journal of Pathology, Vol. 173, No. 3, 09.2008, p. 892-900.

Research output: Contribution to journalArticle

Noubade, R, Del Rio, R, McElvany, B, Zachary, JF, Millward, JM, Wagner, DD, Offner, H, Blankenhorn, EP & Teuscher, C 2008, 'Von-Willebrand factor influences blood brain barrier permeability and brain inflammation in experimental allergic encephalomyelitis', American Journal of Pathology, vol. 173, no. 3, pp. 892-900. https://doi.org/10.2353/ajpath.2008.080001
Noubade, Rajkumar ; Del Rio, Roxana ; McElvany, Benjamin ; Zachary, James F. ; Millward, Jason M. ; Wagner, Denisa D. ; Offner, Halina ; Blankenhorn, Elizabeth P. ; Teuscher, Cory. / Von-Willebrand factor influences blood brain barrier permeability and brain inflammation in experimental allergic encephalomyelitis. In: American Journal of Pathology. 2008 ; Vol. 173, No. 3. pp. 892-900.
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