期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 173, 期 3, 页码 892-900出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2008.080001
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资金
- NHLBI NIH HHS [R37 HL041002, R01 HL041002, HL041002] Funding Source: Medline
- NIAID NIH HHS [AI41747, AI45105, R01 AI041747, P01 AI045666, AI45666] Funding Source: Medline
- NINDS NIH HHS [R01 NS036526, NS36526] Funding Source: Medline
Weibel-Palade bodies within endothelial cells are secretory granules known to release von Witlebrand Factor (VWF), P-selectin, chemokines, and other stored molecules following histamine exposure. Mice with a disrupted VWF gene (VWFKO) have endothetial 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 perfussis 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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