Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis.

Abstract:

:Disruption of the blood-brain barrier (BBB) underlies the development of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Environmental factors, such as Bordetella pertussis, are thought to sensitize central endothelium to biogenic amines like histamine, thereby leading to increased BBB permeability. B. pertussis-induced histamine sensitization (Bphs) is a monogenic intermediate phenotype of EAE controlled by histamine H(1) receptor (Hrh1/H(1)R). Here, we transgenically overexpressed H(1)R in endothelial cells of Hrh1-KO (H(1)RKO) mice to test the role of endothelial H(1)R directly in Bphs and EAE. Unexpectedly, transgenic H(1)RKO mice expressing endothelial H(1)R under control of the von Willebrand factor promoter (H(1)RKO-vWF(H1R) Tg) were Bphs-resistant. Moreover, H(1)RKO-vWF(H1R) Tg mice exhibited decreased BBB permeability and enhanced protection from EAE compared with H(1)RKO mice. Thus, contrary to prevailing assumptions, our results show that endothelial H(1)R expression reduces BBB permeability, suggesting that endothelial H(1)R signaling may be important in the maintenance of cerebrovascular integrity.

authors

Lu C,Diehl SA,Noubade R,Ledoux J,Nelson MT,Spach K,Zachary JF,Blankenhorn EP,Teuscher C

doi

10.1073/pnas.1008816107

subject

Has Abstract

pub_date

2010-11-02 00:00:00

pages

18967-72

issue

44

eissn

0027-8424

issn

1091-6490

pii

1008816107

journal_volume

107

pub_type

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