Journal article
Endothelial histamine H1 receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis
Proceedings of the National Academy of Sciences - PNAS, v 107(44), pp 18967-18972
18 Oct 2010
PMID: 20956310
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Endothelial histamine H1 receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis
- Creators
- Changming LuSean A DiehlRajkumar NoubadeJonathan LedouxMark T NelsonKaren SpachJames F ZacharyElizabeth P BlankenhornCory Teuscher
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 107(44), pp 18967-18972
- Publisher
- National Academy of Sciences
- Number of pages
- 6
- Grant note
- National Institutes of Health: AI045666, AI041747, AI058052, NS061014, NS060901, NS036526, NS069628, HL44455, HL089243
We thank John Dodge and Dr. Mercedes Rincon of the University of Vermont Transgenic Core Facility for generation of vWFH1R Tg mice. We thank Drs. David Hill-Eubanks, Diane Jaworski, Laure Case, and Emma Wall for critical reading of the manuscript. This work was supported by National Institutes of Health Grants AI045666, AI041747, AI058052, NS061014, NS060901, NS036526, and NS069628 (to C.T.) and HL44455 and HL089243 (to M.T.N.).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000283749000044
- Scopus ID
- 2-s2.0-78650480308
- Other Identifier
- 991019231725604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology