Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles
Abstract Aims Acute myocardial infarction rapidly increases blood neutrophils (
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| Veröffentlicht in: | Cardiovascular research 2023-03, Vol.119 (1), p.236-251 |
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| creator | Akbar, Naveed Braithwaite, Adam T Corr, Emma M Koelwyn, Graeme J van Solingen, Coen Cochain, Clément Saliba, Antoine-Emmanuel Corbin, Alastair Pezzolla, Daniela Møller Jørgensen, Malene Bæk, Rikke Edgar, Laurienne De Villiers, Carla Gunadasa-Rohling, Mala Banerjee, Abhirup Paget, Daan Lee, Charlotte Hogg, Eleanor Costin, Adam Dhaliwal, Raman Johnson, Errin Krausgruber, Thomas Riepsaame, Joey Melling, Genevieve E Shanmuganathan, Mayooran Bock, Christoph Carter, David R F Channon, Keith M Riley, Paul R Udalova, Irina A Moore, Kathryn J Anthony, Daniel C Choudhury, Robin P |
| description | Abstract
Aims
Acute myocardial infarction rapidly increases blood neutrophils ( |
| doi_str_mv | 10.1093/cvr/cvac012 |
| format | Article |
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Aims
Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 h after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 min) release of extracellular vesicles (EVs), which have emerged as an important means of cell–cell signalling and are thus a potential mechanism for communicating with remote tissues.
Methods and results
Here, we show that injury to the myocardium rapidly mobilizes neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to arrival at the injured tissue. Time course analysis of plasma-EV composition revealed a rapid and selective increase in EVs bearing VCAM-1. These EVs, which were also enriched for miRNA-126, accumulated preferentially in the spleen where they induced local inflammatory gene and chemokine protein expression, and mobilized splenic-neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing, we generated VCAM-1-deficient EC-EVs and showed that its deletion removed the ability of EC-EVs to provoke the mobilization of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model.
Conclusions
Our findings show a novel EV-dependent mechanism for the rapid mobilization of neutrophils to peripheral blood from a splenic reserve and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells.
Graphical Abstract
Graphical Abstract</description><identifier>ISSN: 0008-6363</identifier><identifier>ISSN: 1755-3245</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1093/cvr/cvac012</identifier><identifier>PMID: 35134856</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Animals ; Endothelial Cells - metabolism ; Extracellular Vesicles - metabolism ; Mice ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Myocardial Infarction - metabolism ; Neutrophils - metabolism ; Original ; Vascular Cell Adhesion Molecule-1 - genetics ; Vascular Cell Adhesion Molecule-1 - metabolism</subject><ispartof>Cardiovascular research, 2023-03, Vol.119 (1), p.236-251</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-c46a63aa11ac08f4b829686cf4e78e847d3164fc5535d75d9895432171c4e5a03</citedby><cites>FETCH-LOGICAL-c413t-c46a63aa11ac08f4b829686cf4e78e847d3164fc5535d75d9895432171c4e5a03</cites><orcidid>0000-0001-6565-1486 ; 0000-0002-5817-2003 ; 0000-0002-0340-1745 ; 0000-0002-5357-8231 ; 0000-0001-7308-9286 ; 0000-0003-3228-2172 ; 0000-0001-8198-5128 ; 0000-0003-1381-3863 ; 0000-0003-2505-2547 ; 0000-0002-8046-1688 ; 0000-0003-1380-6655 ; 0000-0002-9045-9020 ; 0000-0002-5146-9250 ; 0000-0001-7893-2324 ; 0000-0001-6091-3088 ; 0000-0001-5334-557X ; 0000-0002-3194-1247 ; 0000-0003-4620-6373 ; 0000-0001-8060-3706 ; 0000-0002-1374-0329 ; 0000-0002-9862-7332 ; 0000-0002-1628-4680 ; 0000-0002-0401-5862</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35134856$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akbar, Naveed</creatorcontrib><creatorcontrib>Braithwaite, Adam T</creatorcontrib><creatorcontrib>Corr, Emma M</creatorcontrib><creatorcontrib>Koelwyn, Graeme J</creatorcontrib><creatorcontrib>van Solingen, Coen</creatorcontrib><creatorcontrib>Cochain, Clément</creatorcontrib><creatorcontrib>Saliba, Antoine-Emmanuel</creatorcontrib><creatorcontrib>Corbin, Alastair</creatorcontrib><creatorcontrib>Pezzolla, Daniela</creatorcontrib><creatorcontrib>Møller Jørgensen, Malene</creatorcontrib><creatorcontrib>Bæk, Rikke</creatorcontrib><creatorcontrib>Edgar, Laurienne</creatorcontrib><creatorcontrib>De Villiers, Carla</creatorcontrib><creatorcontrib>Gunadasa-Rohling, Mala</creatorcontrib><creatorcontrib>Banerjee, Abhirup</creatorcontrib><creatorcontrib>Paget, Daan</creatorcontrib><creatorcontrib>Lee, Charlotte</creatorcontrib><creatorcontrib>Hogg, Eleanor</creatorcontrib><creatorcontrib>Costin, Adam</creatorcontrib><creatorcontrib>Dhaliwal, Raman</creatorcontrib><creatorcontrib>Johnson, Errin</creatorcontrib><creatorcontrib>Krausgruber, Thomas</creatorcontrib><creatorcontrib>Riepsaame, Joey</creatorcontrib><creatorcontrib>Melling, Genevieve E</creatorcontrib><creatorcontrib>Shanmuganathan, Mayooran</creatorcontrib><creatorcontrib>Bock, Christoph</creatorcontrib><creatorcontrib>Carter, David R F</creatorcontrib><creatorcontrib>Channon, Keith M</creatorcontrib><creatorcontrib>Riley, Paul R</creatorcontrib><creatorcontrib>Udalova, Irina A</creatorcontrib><creatorcontrib>Moore, Kathryn J</creatorcontrib><creatorcontrib>Anthony, Daniel C</creatorcontrib><creatorcontrib>Choudhury, Robin P</creatorcontrib><creatorcontrib>Oxford Acute Myocardial Infarction Study (OxAMI)</creatorcontrib><title>Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>Abstract
Aims
Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 h after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 min) release of extracellular vesicles (EVs), which have emerged as an important means of cell–cell signalling and are thus a potential mechanism for communicating with remote tissues.
Methods and results
Here, we show that injury to the myocardium rapidly mobilizes neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to arrival at the injured tissue. Time course analysis of plasma-EV composition revealed a rapid and selective increase in EVs bearing VCAM-1. These EVs, which were also enriched for miRNA-126, accumulated preferentially in the spleen where they induced local inflammatory gene and chemokine protein expression, and mobilized splenic-neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing, we generated VCAM-1-deficient EC-EVs and showed that its deletion removed the ability of EC-EVs to provoke the mobilization of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model.
Conclusions
Our findings show a novel EV-dependent mechanism for the rapid mobilization of neutrophils to peripheral blood from a splenic reserve and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells.
Graphical Abstract
Graphical Abstract</description><subject>Animals</subject><subject>Endothelial Cells - metabolism</subject><subject>Extracellular Vesicles - metabolism</subject><subject>Mice</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Myocardial Infarction - metabolism</subject><subject>Neutrophils - metabolism</subject><subject>Original</subject><subject>Vascular Cell Adhesion Molecule-1 - genetics</subject><subject>Vascular Cell Adhesion Molecule-1 - 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neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles</title><author>Akbar, Naveed ; Braithwaite, Adam T ; Corr, Emma M ; Koelwyn, Graeme J ; van Solingen, Coen ; Cochain, Clément ; Saliba, Antoine-Emmanuel ; Corbin, Alastair ; Pezzolla, Daniela ; Møller Jørgensen, Malene ; Bæk, Rikke ; Edgar, Laurienne ; De Villiers, Carla ; Gunadasa-Rohling, Mala ; Banerjee, Abhirup ; Paget, Daan ; Lee, Charlotte ; Hogg, Eleanor ; Costin, Adam ; Dhaliwal, Raman ; Johnson, Errin ; Krausgruber, Thomas ; Riepsaame, Joey ; Melling, Genevieve E ; Shanmuganathan, Mayooran ; Bock, Christoph ; Carter, David R F ; Channon, Keith M ; Riley, Paul R ; Udalova, Irina A ; Moore, Kathryn J ; Anthony, Daniel C ; Choudhury, Robin 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research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akbar, Naveed</au><au>Braithwaite, Adam T</au><au>Corr, Emma M</au><au>Koelwyn, Graeme J</au><au>van Solingen, Coen</au><au>Cochain, Clément</au><au>Saliba, Antoine-Emmanuel</au><au>Corbin, Alastair</au><au>Pezzolla, Daniela</au><au>Møller Jørgensen, Malene</au><au>Bæk, Rikke</au><au>Edgar, Laurienne</au><au>De Villiers, Carla</au><au>Gunadasa-Rohling, Mala</au><au>Banerjee, Abhirup</au><au>Paget, Daan</au><au>Lee, Charlotte</au><au>Hogg, Eleanor</au><au>Costin, Adam</au><au>Dhaliwal, Raman</au><au>Johnson, Errin</au><au>Krausgruber, Thomas</au><au>Riepsaame, Joey</au><au>Melling, Genevieve E</au><au>Shanmuganathan, Mayooran</au><au>Bock, Christoph</au><au>Carter, David R F</au><au>Channon, Keith M</au><au>Riley, Paul R</au><au>Udalova, Irina A</au><au>Moore, Kathryn J</au><au>Anthony, Daniel C</au><au>Choudhury, Robin P</au><aucorp>Oxford Acute Myocardial Infarction Study (OxAMI)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2023-03-17</date><risdate>2023</risdate><volume>119</volume><issue>1</issue><spage>236</spage><epage>251</epage><pages>236-251</pages><issn>0008-6363</issn><issn>1755-3245</issn><eissn>1755-3245</eissn><abstract>Abstract
Aims
Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 h after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 min) release of extracellular vesicles (EVs), which have emerged as an important means of cell–cell signalling and are thus a potential mechanism for communicating with remote tissues.
Methods and results
Here, we show that injury to the myocardium rapidly mobilizes neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to arrival at the injured tissue. Time course analysis of plasma-EV composition revealed a rapid and selective increase in EVs bearing VCAM-1. These EVs, which were also enriched for miRNA-126, accumulated preferentially in the spleen where they induced local inflammatory gene and chemokine protein expression, and mobilized splenic-neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing, we generated VCAM-1-deficient EC-EVs and showed that its deletion removed the ability of EC-EVs to provoke the mobilization of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model.
Conclusions
Our findings show a novel EV-dependent mechanism for the rapid mobilization of neutrophils to peripheral blood from a splenic reserve and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells.
Graphical Abstract
Graphical Abstract</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>35134856</pmid><doi>10.1093/cvr/cvac012</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-6565-1486</orcidid><orcidid>https://orcid.org/0000-0002-5817-2003</orcidid><orcidid>https://orcid.org/0000-0002-0340-1745</orcidid><orcidid>https://orcid.org/0000-0002-5357-8231</orcidid><orcidid>https://orcid.org/0000-0001-7308-9286</orcidid><orcidid>https://orcid.org/0000-0003-3228-2172</orcidid><orcidid>https://orcid.org/0000-0001-8198-5128</orcidid><orcidid>https://orcid.org/0000-0003-1381-3863</orcidid><orcidid>https://orcid.org/0000-0003-2505-2547</orcidid><orcidid>https://orcid.org/0000-0002-8046-1688</orcidid><orcidid>https://orcid.org/0000-0003-1380-6655</orcidid><orcidid>https://orcid.org/0000-0002-9045-9020</orcidid><orcidid>https://orcid.org/0000-0002-5146-9250</orcidid><orcidid>https://orcid.org/0000-0001-7893-2324</orcidid><orcidid>https://orcid.org/0000-0001-6091-3088</orcidid><orcidid>https://orcid.org/0000-0001-5334-557X</orcidid><orcidid>https://orcid.org/0000-0002-3194-1247</orcidid><orcidid>https://orcid.org/0000-0003-4620-6373</orcidid><orcidid>https://orcid.org/0000-0001-8060-3706</orcidid><orcidid>https://orcid.org/0000-0002-1374-0329</orcidid><orcidid>https://orcid.org/0000-0002-9862-7332</orcidid><orcidid>https://orcid.org/0000-0002-1628-4680</orcidid><orcidid>https://orcid.org/0000-0002-0401-5862</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-6363 |
| ispartof | Cardiovascular research, 2023-03, Vol.119 (1), p.236-251 |
| issn | 0008-6363 1755-3245 1755-3245 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10022859 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Endothelial Cells - metabolism Extracellular Vesicles - metabolism Mice MicroRNAs - genetics MicroRNAs - metabolism Myocardial Infarction - metabolism Neutrophils - metabolism Original Vascular Cell Adhesion Molecule-1 - genetics Vascular Cell Adhesion Molecule-1 - metabolism |
| title | Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T14%3A12%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rapid%20neutrophil%20mobilization%20by%20VCAM-1+%20endothelial%20cell-derived%20extracellular%20vesicles&rft.jtitle=Cardiovascular%20research&rft.au=Akbar,%20Naveed&rft.aucorp=Oxford%20Acute%20Myocardial%20Infarction%20Study%20(OxAMI)&rft.date=2023-03-17&rft.volume=119&rft.issue=1&rft.spage=236&rft.epage=251&rft.pages=236-251&rft.issn=0008-6363&rft.eissn=1755-3245&rft_id=info:doi/10.1093/cvr/cvac012&rft_dat=%3Cproquest_pubme%3E2627137063%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2627137063&rft_id=info:pmid/35134856&rft_oup_id=10.1093/cvr/cvac012&rfr_iscdi=true |