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- PMID: 20956310
- UKPMCID: 20956310
- DOI: 10.1073/pnas.1008816107
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Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis.
Lu, Changming; Diehl, Sean A; Noubade, Rajkumar; Ledoux, Jonathan; Nelson, Mark T; Spach, Karen; Zachary, James F; Blankenhorn, Elizabeth P; Teuscher, Cory
Proceedings of the National Academy of Sciences of the United States of America. 2010;107(44):18967-72.
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Full-text held externally
- PMID: 20956310
- UKPMCID: 20956310
- DOI: 10.1073/pnas.1008816107
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.
Bibliographic metadata
- AI041747, NIAID NIH HHS, United States
- AI045666, NIAID NIH HHS, United States
- AI058052, NIAID NIH HHS, United States
- HL089243, NHLBI NIH HHS, United States
- HL44455, NHLBI NIH HHS, United States
- NS036526, NINDS NIH HHS, United States
- NS060901, NINDS NIH HHS, United States
- NS061014, NINDS NIH HHS, United States
- NS069628, NINDS NIH HHS, United States