Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin
Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through...
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creator | Nussbaum, Claudia Bannenberg, Sarah Keul, Petra Gräler, Markus H. Gonçalves-de-Albuquerque, Cassiano F. Korhonen, Hanna von Wnuck Lipinski, Karin Heusch, Gerd de Castro Faria Neto, Hugo C. Rohwedder, Ina Göthert, Joachim R. Prasad, Vysakh Pushpa Haufe, Günter Lange-Sperandio, Baerbel Offermanns, Stefan Sperandio, Markus Levkau, Bodo |
description | Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P
3
) and Gα
q
, PLCβ and Ca
2+
. Intra-arterial S1P administration increases leukocyte rolling, while S1P
3
deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P
3
. Histamine and epinephrine require S1P
3
for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P
1
inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific
S1P
1
−/−
mice. In agreement with a dominant pro-rolling effect of S1P
3
, FTY720 inhibits rolling in control and
S1P
1
−/−
but not in
S1P
3
−/−
mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action.
The lipid sphingosine-1-phosphate (S1P) is known to mediate leukocyte recruitment in inflammation. Here, Nussbaum
et al.
show that S1P, via its receptor S1P3, also regulates leukocyte rolling on endothelium by promoting the presentation of the adhesion molecule P-selectin on the endothelial surface. |
doi_str_mv | 10.1038/ncomms7416 |
format | Article |
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3
) and Gα
q
, PLCβ and Ca
2+
. Intra-arterial S1P administration increases leukocyte rolling, while S1P
3
deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P
3
. Histamine and epinephrine require S1P
3
for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P
1
inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific
S1P
1
−/−
mice. In agreement with a dominant pro-rolling effect of S1P
3
, FTY720 inhibits rolling in control and
S1P
1
−/−
but not in
S1P
3
−/−
mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action.
The lipid sphingosine-1-phosphate (S1P) is known to mediate leukocyte recruitment in inflammation. Here, Nussbaum
et al.
show that S1P, via its receptor S1P3, also regulates leukocyte rolling on endothelium by promoting the presentation of the adhesion molecule P-selectin on the endothelial surface.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms7416</identifier><identifier>PMID: 25832730</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/31 ; 13/51 ; 13/95 ; 14/1 ; 14/63 ; 631/250/249/2510/2100 ; 631/45/287/1196 ; 631/80/79 ; 64/110 ; 64/60 ; 692/698/1543/1565/1597 ; Animals ; Calcium - metabolism ; Endothelium, Vascular - metabolism ; Epinephrine - metabolism ; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism ; Histamine - metabolism ; Human Umbilical Vein Endothelial Cells ; Humanities and Social Sciences ; Humans ; Immunohistochemistry ; Leukocyte Rolling - genetics ; Lysophospholipids - metabolism ; Male ; Mast Cells - metabolism ; Mice ; Mice, Knockout ; multidisciplinary ; Muscle, Skeletal - blood supply ; P-Selectin - metabolism ; Phospholipase C beta - metabolism ; Phosphotransferases (Alcohol Group Acceptor) - metabolism ; Receptors, Lysosphingolipid - genetics ; Receptors, Lysosphingolipid - metabolism ; Science ; Science (multidisciplinary) ; Sphingosine - analogs & derivatives ; Sphingosine - metabolism ; Venules</subject><ispartof>Nature communications, 2015-04, Vol.6 (1), p.6416-6416, Article 6416</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Apr 2015</rights><rights>Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-5f3a87fb54dc917029eec5842174e677327ae02337885a82016475c974918c893</citedby><cites>FETCH-LOGICAL-c508t-5f3a87fb54dc917029eec5842174e677327ae02337885a82016475c974918c893</cites><orcidid>0000-0002-7689-3613 ; 0000000276893613</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396399/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396399/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25832730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nussbaum, Claudia</creatorcontrib><creatorcontrib>Bannenberg, Sarah</creatorcontrib><creatorcontrib>Keul, Petra</creatorcontrib><creatorcontrib>Gräler, Markus H.</creatorcontrib><creatorcontrib>Gonçalves-de-Albuquerque, Cassiano F.</creatorcontrib><creatorcontrib>Korhonen, Hanna</creatorcontrib><creatorcontrib>von Wnuck Lipinski, Karin</creatorcontrib><creatorcontrib>Heusch, Gerd</creatorcontrib><creatorcontrib>de Castro Faria Neto, Hugo C.</creatorcontrib><creatorcontrib>Rohwedder, Ina</creatorcontrib><creatorcontrib>Göthert, Joachim R.</creatorcontrib><creatorcontrib>Prasad, Vysakh Pushpa</creatorcontrib><creatorcontrib>Haufe, Günter</creatorcontrib><creatorcontrib>Lange-Sperandio, Baerbel</creatorcontrib><creatorcontrib>Offermanns, Stefan</creatorcontrib><creatorcontrib>Sperandio, Markus</creatorcontrib><creatorcontrib>Levkau, Bodo</creatorcontrib><title>Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P
3
) and Gα
q
, PLCβ and Ca
2+
. Intra-arterial S1P administration increases leukocyte rolling, while S1P
3
deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P
3
. Histamine and epinephrine require S1P
3
for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P
1
inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific
S1P
1
−/−
mice. In agreement with a dominant pro-rolling effect of S1P
3
, FTY720 inhibits rolling in control and
S1P
1
−/−
but not in
S1P
3
−/−
mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action.
The lipid sphingosine-1-phosphate (S1P) is known to mediate leukocyte recruitment in inflammation. Here, Nussbaum
et al.
show that S1P, via its receptor S1P3, also regulates leukocyte rolling on endothelium by promoting the presentation of the adhesion molecule P-selectin on the endothelial surface.</description><subject>13/31</subject><subject>13/51</subject><subject>13/95</subject><subject>14/1</subject><subject>14/63</subject><subject>631/250/249/2510/2100</subject><subject>631/45/287/1196</subject><subject>631/80/79</subject><subject>64/110</subject><subject>64/60</subject><subject>692/698/1543/1565/1597</subject><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Epinephrine - metabolism</subject><subject>GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism</subject><subject>Histamine - metabolism</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Leukocyte Rolling - genetics</subject><subject>Lysophospholipids - metabolism</subject><subject>Male</subject><subject>Mast Cells - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>multidisciplinary</subject><subject>Muscle, Skeletal - blood supply</subject><subject>P-Selectin - metabolism</subject><subject>Phospholipase C beta - metabolism</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - metabolism</subject><subject>Receptors, Lysosphingolipid - genetics</subject><subject>Receptors, Lysosphingolipid - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - metabolism</subject><subject>Venules</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkV1LHDEYhUOxVFFv-gPKQG9KZTRfM8ncCCJ-gVCh7XXIZN_dic0kYzJTWH-9GVbtWnOThPPk5LwchD4TfEwwkyfehL5PgpP6A9qjmJOSCMp2ts676DCle5wXa4jk_BPapZVkVDC8h9qfQ2f9KiTroSTl0IU0dHqEIoKBYQyxYMUQQx9GSIWD6U8w61kNzuVnRbsu-tBaZx_nG_hFGDtwVrvirkzgwIzWH6CPS-0SHD7v--j35cWv8-vy9sfVzfnZbWkqLMeyWjItxbKt-MI0RGDaAJhKckoEh1qIHFgDpowJKSstKSY1F5VpBM9TGdmwfXS68R2mtoeFAT9G7dQQba_jWgVt1VvF206twl_FWVOzZjb49mwQw8MEaVS9TQac0x7ClBSp60ZyjKs6o1__Q-_DFH0eb6Yk5ZQSkqnvG8rEkFKE5WsYgtXcnvrXXoa_bMd_RV-6ysDRBkhZ8iuIW3--t3sCbgWlYw</recordid><startdate>20150402</startdate><enddate>20150402</enddate><creator>Nussbaum, Claudia</creator><creator>Bannenberg, Sarah</creator><creator>Keul, Petra</creator><creator>Gräler, Markus H.</creator><creator>Gonçalves-de-Albuquerque, Cassiano F.</creator><creator>Korhonen, Hanna</creator><creator>von Wnuck Lipinski, Karin</creator><creator>Heusch, Gerd</creator><creator>de Castro Faria Neto, Hugo C.</creator><creator>Rohwedder, Ina</creator><creator>Göthert, Joachim R.</creator><creator>Prasad, Vysakh Pushpa</creator><creator>Haufe, Günter</creator><creator>Lange-Sperandio, Baerbel</creator><creator>Offermanns, Stefan</creator><creator>Sperandio, Markus</creator><creator>Levkau, Bodo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Pub. 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metabolism</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Epinephrine - metabolism</topic><topic>GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism</topic><topic>Histamine - metabolism</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Leukocyte Rolling - genetics</topic><topic>Lysophospholipids - metabolism</topic><topic>Male</topic><topic>Mast Cells - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>multidisciplinary</topic><topic>Muscle, Skeletal - blood supply</topic><topic>P-Selectin - metabolism</topic><topic>Phospholipase C beta - metabolism</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - metabolism</topic><topic>Receptors, Lysosphingolipid - genetics</topic><topic>Receptors, Lysosphingolipid - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine - metabolism</topic><topic>Venules</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nussbaum, Claudia</creatorcontrib><creatorcontrib>Bannenberg, Sarah</creatorcontrib><creatorcontrib>Keul, Petra</creatorcontrib><creatorcontrib>Gräler, Markus H.</creatorcontrib><creatorcontrib>Gonçalves-de-Albuquerque, Cassiano F.</creatorcontrib><creatorcontrib>Korhonen, Hanna</creatorcontrib><creatorcontrib>von Wnuck Lipinski, Karin</creatorcontrib><creatorcontrib>Heusch, Gerd</creatorcontrib><creatorcontrib>de Castro Faria Neto, Hugo C.</creatorcontrib><creatorcontrib>Rohwedder, Ina</creatorcontrib><creatorcontrib>Göthert, Joachim R.</creatorcontrib><creatorcontrib>Prasad, Vysakh Pushpa</creatorcontrib><creatorcontrib>Haufe, Günter</creatorcontrib><creatorcontrib>Lange-Sperandio, Baerbel</creatorcontrib><creatorcontrib>Offermanns, Stefan</creatorcontrib><creatorcontrib>Sperandio, Markus</creatorcontrib><creatorcontrib>Levkau, Bodo</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nussbaum, Claudia</au><au>Bannenberg, Sarah</au><au>Keul, Petra</au><au>Gräler, Markus H.</au><au>Gonçalves-de-Albuquerque, Cassiano F.</au><au>Korhonen, Hanna</au><au>von Wnuck Lipinski, Karin</au><au>Heusch, Gerd</au><au>de Castro Faria Neto, Hugo C.</au><au>Rohwedder, Ina</au><au>Göthert, Joachim R.</au><au>Prasad, Vysakh Pushpa</au><au>Haufe, Günter</au><au>Lange-Sperandio, Baerbel</au><au>Offermanns, Stefan</au><au>Sperandio, Markus</au><au>Levkau, Bodo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2015-04-02</date><risdate>2015</risdate><volume>6</volume><issue>1</issue><spage>6416</spage><epage>6416</epage><pages>6416-6416</pages><artnum>6416</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P
3
) and Gα
q
, PLCβ and Ca
2+
. Intra-arterial S1P administration increases leukocyte rolling, while S1P
3
deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P
3
. Histamine and epinephrine require S1P
3
for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P
1
inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific
S1P
1
−/−
mice. In agreement with a dominant pro-rolling effect of S1P
3
, FTY720 inhibits rolling in control and
S1P
1
−/−
but not in
S1P
3
−/−
mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action.
The lipid sphingosine-1-phosphate (S1P) is known to mediate leukocyte recruitment in inflammation. Here, Nussbaum
et al.
show that S1P, via its receptor S1P3, also regulates leukocyte rolling on endothelium by promoting the presentation of the adhesion molecule P-selectin on the endothelial surface.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25832730</pmid><doi>10.1038/ncomms7416</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-7689-3613</orcidid><orcidid>https://orcid.org/0000000276893613</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2041-1723 |
ispartof | Nature communications, 2015-04, Vol.6 (1), p.6416-6416, Article 6416 |
issn | 2041-1723 2041-1723 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4396399 |
source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Springer Nature OA Free Journals |
subjects | 13/31 13/51 13/95 14/1 14/63 631/250/249/2510/2100 631/45/287/1196 631/80/79 64/110 64/60 692/698/1543/1565/1597 Animals Calcium - metabolism Endothelium, Vascular - metabolism Epinephrine - metabolism GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism Histamine - metabolism Human Umbilical Vein Endothelial Cells Humanities and Social Sciences Humans Immunohistochemistry Leukocyte Rolling - genetics Lysophospholipids - metabolism Male Mast Cells - metabolism Mice Mice, Knockout multidisciplinary Muscle, Skeletal - blood supply P-Selectin - metabolism Phospholipase C beta - metabolism Phosphotransferases (Alcohol Group Acceptor) - metabolism Receptors, Lysosphingolipid - genetics Receptors, Lysosphingolipid - metabolism Science Science (multidisciplinary) Sphingosine - analogs & derivatives Sphingosine - metabolism Venules |
title | Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin |
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