Endothelial histamine H₁ receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis
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 inc...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2010-11, Vol.107 (44), p.18967-18972 |
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| creator | Lu, Changming Diehl, Sean A Noubade, Rajkumar Ledoux, Jonathan Nelson, Mark T Spach, Karen Zachary, James F Blankenhorn, Elizabeth P Teuscher, Cory |
| description | 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 H₁ receptor (Hrh1/H₁R). Here, we transgenically overexpressed H₁R in endothelial cells of Hrh1-KO (H₁RKO) mice to test the role of endothelial H₁R directly in Bphs and EAE. Unexpectedly, transgenic H₁RKO mice expressing endothelial H₁R under control of the von Willebrand factor promoter (H₁RKO-vWFH¹R Tg) were Bphs-resistant. Moreover, H₁RKO-vWFH¹R Tg mice exhibited decreased BBB permeability and enhanced protection from EAE compared with H₁RKO mice. Thus, contrary to prevailing assumptions, our results show that endothelial H₁R expression reduces BBB permeability, suggesting that endothelial H₁R signaling may be important in the maintenance of cerebrovascular integrity. |
| doi_str_mv | 10.1073/pnas.1008816107 |
| format | Article |
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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 H₁ receptor (Hrh1/H₁R). Here, we transgenically overexpressed H₁R in endothelial cells of Hrh1-KO (H₁RKO) mice to test the role of endothelial H₁R directly in Bphs and EAE. Unexpectedly, transgenic H₁RKO mice expressing endothelial H₁R under control of the von Willebrand factor promoter (H₁RKO-vWFH¹R Tg) were Bphs-resistant. Moreover, H₁RKO-vWFH¹R Tg mice exhibited decreased BBB permeability and enhanced protection from EAE compared with H₁RKO mice. Thus, contrary to prevailing assumptions, our results show that endothelial H₁R expression reduces BBB permeability, suggesting that endothelial H₁R signaling may be important in the maintenance of cerebrovascular integrity.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1008816107</identifier><identifier>PMID: 20956310</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Biogenic amines ; Biological Sciences ; Blood brain barrier ; Blood-Brain Barrier - metabolism ; Bordetella pertussis ; Bordetella pertussis - genetics ; Bordetella pertussis - metabolism ; Capillary Permeability ; Central nervous system ; Encephalomyelitis, Autoimmune, Experimental - genetics ; Encephalomyelitis, Autoimmune, Experimental - metabolism ; Endothelial cells ; Endothelium ; Endothelium, Vascular - metabolism ; Environmental factors ; Experimental allergic encephalomyelitis ; Experimental autoimmune encephalomyelitis ; Genetic Predisposition to Disease ; Histamine ; Histamine H1 receptors ; Histamines ; Mast cells ; Membrane permeability ; Mice ; Mice, Knockout ; Multiple sclerosis ; Multiple Sclerosis - genetics ; Multiple Sclerosis - metabolism ; Neurons ; Pertussis ; Promoters ; Receptors ; Receptors, Histamine H1 - genetics ; Receptors, Histamine H1 - metabolism ; Signal Transduction ; T lymphocytes ; Transgenic mice ; Von Willebrand factor ; von Willebrand Factor - genetics ; von Willebrand Factor - metabolism ; Whooping Cough - genetics ; Whooping Cough - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2010-11, Vol.107 (44), p.18967-18972</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/107/44.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25748605$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25748605$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20956310$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Changming</creatorcontrib><creatorcontrib>Diehl, Sean A</creatorcontrib><creatorcontrib>Noubade, Rajkumar</creatorcontrib><creatorcontrib>Ledoux, Jonathan</creatorcontrib><creatorcontrib>Nelson, Mark T</creatorcontrib><creatorcontrib>Spach, Karen</creatorcontrib><creatorcontrib>Zachary, James F</creatorcontrib><creatorcontrib>Blankenhorn, Elizabeth P</creatorcontrib><creatorcontrib>Teuscher, Cory</creatorcontrib><title>Endothelial histamine H₁ receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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 H₁ receptor (Hrh1/H₁R). Here, we transgenically overexpressed H₁R in endothelial cells of Hrh1-KO (H₁RKO) mice to test the role of endothelial H₁R directly in Bphs and EAE. Unexpectedly, transgenic H₁RKO mice expressing endothelial H₁R under control of the von Willebrand factor promoter (H₁RKO-vWFH¹R Tg) were Bphs-resistant. Moreover, H₁RKO-vWFH¹R Tg mice exhibited decreased BBB permeability and enhanced protection from EAE compared with H₁RKO mice. Thus, contrary to prevailing assumptions, our results show that endothelial H₁R expression reduces BBB permeability, suggesting that endothelial H₁R signaling may be important in the maintenance of cerebrovascular integrity.</description><subject>Animals</subject><subject>Biogenic amines</subject><subject>Biological Sciences</subject><subject>Blood brain barrier</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Bordetella pertussis</subject><subject>Bordetella pertussis - genetics</subject><subject>Bordetella pertussis - metabolism</subject><subject>Capillary Permeability</subject><subject>Central nervous system</subject><subject>Encephalomyelitis, Autoimmune, Experimental - genetics</subject><subject>Encephalomyelitis, Autoimmune, Experimental - metabolism</subject><subject>Endothelial cells</subject><subject>Endothelium</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Environmental factors</subject><subject>Experimental allergic encephalomyelitis</subject><subject>Experimental autoimmune encephalomyelitis</subject><subject>Genetic Predisposition to Disease</subject><subject>Histamine</subject><subject>Histamine H1 receptors</subject><subject>Histamines</subject><subject>Mast cells</subject><subject>Membrane permeability</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - genetics</subject><subject>Multiple Sclerosis - metabolism</subject><subject>Neurons</subject><subject>Pertussis</subject><subject>Promoters</subject><subject>Receptors</subject><subject>Receptors, Histamine H1 - genetics</subject><subject>Receptors, Histamine H1 - metabolism</subject><subject>Signal Transduction</subject><subject>T lymphocytes</subject><subject>Transgenic mice</subject><subject>Von Willebrand factor</subject><subject>von Willebrand Factor - genetics</subject><subject>von Willebrand Factor - metabolism</subject><subject>Whooping Cough - genetics</subject><subject>Whooping Cough - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUj1vFDEQXSEQOQI1FeCOamH87W2QUJQQpEgUkNry7nrvHHntw_ZGuhI6_mZ-CT7dEaCCyqP3nt688UzTPMfwBoOkb7fB5FqBUlhU4EGzwtDhVrAOHjYrACJbxQg7aZ7kfAMAHVfwuDkhtRAUw6r5cR7GWDbWO-PRxuViZhcsurz7_g0lO9htiQlltw7Gu7Cu0LgMNqPexzi2fTIuoN6k5GxCW5tma3rnXdkhE0aUl7w3cEeoRGSWEt08L7WDDZXbGB_nXW1eXH7aPJqMz_bZ8T1tri_Ov5xdtlefPnw8e3_VThTz0na467kcLJ6EFMB7InpsyCgHSqYB48lKSkBZq6Slkxhg4JKMzEjOe8kkCHravDv4bpd-tuNgQ0nG621ys0k7HY3TfzPBbfQ63mrSSaqUrAavjwYpfl1sLnp2dVDvTbBxyVpxIbniDP5PKSWj_1RKQZgCIfbxX_4Z_z73r5VWAToK6m3c0_U4NGMaq07sJ3hxkNzkut7fFlwyVf-08q8O_GSiNuvksr7-TABTwB1IwiT9CbVZxdw</recordid><startdate>20101102</startdate><enddate>20101102</enddate><creator>Lu, Changming</creator><creator>Diehl, Sean A</creator><creator>Noubade, Rajkumar</creator><creator>Ledoux, Jonathan</creator><creator>Nelson, Mark T</creator><creator>Spach, Karen</creator><creator>Zachary, James F</creator><creator>Blankenhorn, Elizabeth P</creator><creator>Teuscher, Cory</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20101102</creationdate><title>Endothelial histamine H₁ receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis</title><author>Lu, Changming ; Diehl, Sean A ; Noubade, Rajkumar ; Ledoux, Jonathan ; Nelson, Mark T ; Spach, Karen ; Zachary, James F ; Blankenhorn, Elizabeth P ; Teuscher, Cory</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-f315t-919b57ce1f67605b26b1a2d7c32fc11fe73208ee87e3f6c0c572d4a755b747063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biogenic amines</topic><topic>Biological Sciences</topic><topic>Blood brain barrier</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Bordetella pertussis</topic><topic>Bordetella pertussis - genetics</topic><topic>Bordetella pertussis - metabolism</topic><topic>Capillary Permeability</topic><topic>Central nervous system</topic><topic>Encephalomyelitis, Autoimmune, Experimental - genetics</topic><topic>Encephalomyelitis, Autoimmune, Experimental - metabolism</topic><topic>Endothelial cells</topic><topic>Endothelium</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Environmental factors</topic><topic>Experimental allergic encephalomyelitis</topic><topic>Experimental autoimmune encephalomyelitis</topic><topic>Genetic Predisposition to Disease</topic><topic>Histamine</topic><topic>Histamine H1 receptors</topic><topic>Histamines</topic><topic>Mast cells</topic><topic>Membrane permeability</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - genetics</topic><topic>Multiple Sclerosis - metabolism</topic><topic>Neurons</topic><topic>Pertussis</topic><topic>Promoters</topic><topic>Receptors</topic><topic>Receptors, Histamine H1 - genetics</topic><topic>Receptors, Histamine H1 - metabolism</topic><topic>Signal Transduction</topic><topic>T lymphocytes</topic><topic>Transgenic mice</topic><topic>Von Willebrand factor</topic><topic>von Willebrand Factor - genetics</topic><topic>von Willebrand Factor - metabolism</topic><topic>Whooping Cough - genetics</topic><topic>Whooping Cough - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Changming</creatorcontrib><creatorcontrib>Diehl, Sean A</creatorcontrib><creatorcontrib>Noubade, Rajkumar</creatorcontrib><creatorcontrib>Ledoux, Jonathan</creatorcontrib><creatorcontrib>Nelson, Mark T</creatorcontrib><creatorcontrib>Spach, Karen</creatorcontrib><creatorcontrib>Zachary, James F</creatorcontrib><creatorcontrib>Blankenhorn, Elizabeth P</creatorcontrib><creatorcontrib>Teuscher, Cory</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Changming</au><au>Diehl, Sean A</au><au>Noubade, Rajkumar</au><au>Ledoux, Jonathan</au><au>Nelson, Mark T</au><au>Spach, Karen</au><au>Zachary, James F</au><au>Blankenhorn, Elizabeth P</au><au>Teuscher, Cory</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endothelial histamine H₁ receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2010-11-02</date><risdate>2010</risdate><volume>107</volume><issue>44</issue><spage>18967</spage><epage>18972</epage><pages>18967-18972</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><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 H₁ receptor (Hrh1/H₁R). Here, we transgenically overexpressed H₁R in endothelial cells of Hrh1-KO (H₁RKO) mice to test the role of endothelial H₁R directly in Bphs and EAE. Unexpectedly, transgenic H₁RKO mice expressing endothelial H₁R under control of the von Willebrand factor promoter (H₁RKO-vWFH¹R Tg) were Bphs-resistant. Moreover, H₁RKO-vWFH¹R Tg mice exhibited decreased BBB permeability and enhanced protection from EAE compared with H₁RKO mice. Thus, contrary to prevailing assumptions, our results show that endothelial H₁R expression reduces BBB permeability, suggesting that endothelial H₁R signaling may be important in the maintenance of cerebrovascular integrity.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>20956310</pmid><doi>10.1073/pnas.1008816107</doi><tpages>6</tpages></addata></record> |
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| subjects | Animals Biogenic amines Biological Sciences Blood brain barrier Blood-Brain Barrier - metabolism Bordetella pertussis Bordetella pertussis - genetics Bordetella pertussis - metabolism Capillary Permeability Central nervous system Encephalomyelitis, Autoimmune, Experimental - genetics Encephalomyelitis, Autoimmune, Experimental - metabolism Endothelial cells Endothelium Endothelium, Vascular - metabolism Environmental factors Experimental allergic encephalomyelitis Experimental autoimmune encephalomyelitis Genetic Predisposition to Disease Histamine Histamine H1 receptors Histamines Mast cells Membrane permeability Mice Mice, Knockout Multiple sclerosis Multiple Sclerosis - genetics Multiple Sclerosis - metabolism Neurons Pertussis Promoters Receptors Receptors, Histamine H1 - genetics Receptors, Histamine H1 - metabolism Signal Transduction T lymphocytes Transgenic mice Von Willebrand factor von Willebrand Factor - genetics von Willebrand Factor - metabolism Whooping Cough - genetics Whooping Cough - metabolism |
| title | Endothelial histamine H₁ receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis |
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