{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:26:57Z","timestamp":1790774817435,"version":"4.1.0"},"reference-count":36,"publisher":"Georg Thieme Verlag KG","issue":"05","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EFS"},{"name":"ARMESA"},{"name":"SFH"},{"DOI":"10.13039\/501100002261","name":"RFBR","doi-asserted-by":"crossref","award":["19-34-9003 9"],"award-info":[{"award-number":["19-34-9003 9"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Objective\u2003Integrins are key regulators of various platelet functions. The pathophysiological importance of most platelet integrins has been investigated, with the exception of \u03b15\u03b21, a receptor for fibronectin. The aim of this study was to characterize the role of \u03b15\u03b21 in megakaryopoiesis, platelet function, and to determine its importance in hemostasis and arterial thrombosis.<\/jats:p><jats:p>\n          Approach and Results\u2003We generated a mouse strain deficient for integrin \u03b15\u03b21 on megakaryocytes and platelets (PF4Cre-\u03b15\u2212\/\u2212). PF4Cre-\u03b15\u2212\/\u2212 mice were viable, fertile, and presented no apparent signs of abnormality. Megakaryopoiesis appears unaltered as evidence by a normal megakaryocyte morphology and development, which is in agreement with a normal platelet count. Expression of the main platelet receptors and the response of PF4Cre-\u03b15\u2212\/\u2212 platelets to a series of agonists were all completely normal. Adhesion and aggregation of PF4Cre-\u03b15\u2212\/\u2212 platelets under shear flow on fibrinogen, laminin, or von Willebrand factor were unimpaired. In contrast, PF4Cre-\u03b15\u2212\/\u2212 platelets displayed a marked decrease in adhesion, activation, and aggregation on fibrillar cellular fibronectin and collagen. PF4Cre-\u03b15\u2212\/\u2212 mice presented no defect in a tail-bleeding time assay and no increase in inflammatory bleeding in a reverse passive Arthus model and a lipopolysaccharide pulmonary inflammation model. Finally, no defects were observed in three distinct experimental models of arterial thrombosis based on ferric chloride-induced injury of the carotid artery, mechanical injury of the abdominal aorta, or laser-induced injury of mesenteric vessels.<\/jats:p><jats:p>\n          Conclusion\u2003In summary, this study shows that platelet integrin \u03b15\u03b21 is a key receptor for fibrillar cellular fibronectin but is dispensable in hemostasis and arterial thrombosis.<\/jats:p>","DOI":"10.1055\/a-1659-6214","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T23:11:53Z","timestamp":1633129913000},"page":"767-776","source":"Crossref","is-referenced-by-count":18,"title":["Characterization of the Role of Integrin \u03b15\u03b21 in Platelet Function, Hemostasis, and Experimental Thrombosis"],"prefix":"10.1055","volume":"122","author":[{"given":"Emily","family":"Janus-Bell","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Yakusheva","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"},{"name":"Center for Theoretical Problems of Physicochemical Pharmacology, Cellular Hemostasis Lab, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Scandola","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Receveur","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usman Muhammad","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Mouriaux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Bourdon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Loubi\u00e8re","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Eckly","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotis A.","family":"Senis","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail A.","family":"Panteleev","sequence":"additional","affiliation":[{"name":"Center for Theoretical Problems of Physicochemical Pharmacology, Cellular Hemostasis Lab, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gachet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre H.","family":"Mangin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"issue":"10","key":"ref1","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.1182\/blood-2007-11-123620","article-title":"Inflammation induces hemorrhage in thrombocytopenia","volume":"111","author":"T Goerge","year":"2008","journal-title":"Blood"},{"issue":"11","key":"ref2","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.2515","article-title":"Arterial thrombosis\u2013insidious, unpredictable and deadly","volume":"17","author":"S P Jackson","year":"2011","journal-title":"Nat Med"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0092-8674(00)80983-6","article-title":"Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor","volume":"84","author":"B Savage","year":"1996","journal-title":"Cell"},{"issue":"05","key":"ref4","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0092-8674(00)81607-4","article-title":"Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow","volume":"94","author":"B Savage","year":"1998","journal-title":"Cell"},{"issue":"12","key":"ref5","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1111\/jth.12009","article-title":"The future of glycoprotein VI as an antithrombotic target","volume":"10","author":"M Zahid","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1152\/physrev.00016.2011","article-title":"New fundamentals in hemostasis","volume":"93","author":"H H Versteeg","year":"2013","journal-title":"Physiol Rev"},{"issue":"03","key":"ref7","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1182\/blood.V88.3.907.907","article-title":"Analysis of GPIIb\/IIIa receptor number by quantification of 7E3 binding to human platelets","volume":"88","author":"C L Wagner","year":"1996","journal-title":"Blood"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1750-1172-1-10","article-title":"Glanzmann thrombasthenia","volume":"1","author":"A T Nurden","year":"2006","journal-title":"Orphanet J Rare Dis"},{"issue":"07","key":"ref9","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1160\/TH16-12-0911","article-title":"Platelet receptors as therapeutic targets: past, present and future","volume":"117","author":"J Jamasbi","year":"2017","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"e55094","DOI":"10.1371\/journal.pone.0055094","article-title":"Conditional knockout of integrin \u03b12\u03b21 in murine megakaryocytes leads to reduced mean platelet volume","volume":"8","author":"D Habart","year":"2013","journal-title":"PLoS One"},{"issue":"05","key":"ref11","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1161\/CIRCULATIONAHA.112.000799","article-title":"Integrin \u03b16\u03b21 is the main receptor for vascular laminins and plays a role in platelet adhesion, activation, and arterial thrombosis","volume":"128","author":"M Schaff","year":"2013","journal-title":"Circulation"},{"issue":"10","key":"ref12","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1182\/blood-2003-04-1323","article-title":"The contributions of the alpha 2 beta 1 integrin to vascular thrombosis in vivo","volume":"102","author":"L He","year":"2003","journal-title":"Blood"},{"issue":"06","key":"ref13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1096\/fj.02-0381fje","article-title":"Complementary roles of glycoprotein VI and alpha2beta1 integrin in collagen-induced thrombus formation in flowing whole blood ex vivo","volume":"17","author":"M JE Kuijpers","year":"2003","journal-title":"FASEB J"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1242\/dev.119.4.1093","article-title":"Embryonic mesodermal defects in alpha 5 integrin-deficient mice","volume":"119","author":"J T Yang","year":"1993","journal-title":"Development"},{"issue":"11","key":"ref15","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.1182\/blood.V84.11.3724.bloodjournal84113724","article-title":"Platelet adhesion to fibronectin in flow: dependence on surface concentration and shear rate, role of platelet membrane glycoproteins GP IIb\/IIIa and VLA-5, and inhibition by heparin","volume":"84","author":"S Beumer","year":"1994","journal-title":"Blood"},{"issue":"10","key":"ref16","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1111\/j.1538-7836.2004.00925.x","article-title":"Evaluation of the role of platelet integrins in fibronectin-dependent spreading and adhesion","volume":"2","author":"O JT McCarty","year":"2004","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1160\/TH14-11-0958","article-title":"Fibrillar cellular fibronectin supports efficient platelet aggregation and procoagulant activity","volume":"114","author":"E Maurer","year":"2015","journal-title":"Thromb Haemost"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-1-61779-307-3_13","article-title":"Characterization of megakaryocyte development in the native bone marrow environment","volume":"788","author":"A Eckly","year":"2012","journal-title":"Methods Mol Biol"},{"issue":"18","key":"ref19","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1182\/blood.2019002848","article-title":"Interplay between the tyrosine kinases Chk and Csk and phosphatase PTPRJ is critical for regulating platelets in mice","volume":"135","author":"Z Nagy","year":"2020","journal-title":"Blood"},{"key":"ref20","first-page":"13","article-title":"Preparation of washed platelet suspensions from human and rodent blood","volume":"272","author":"J-P Cazenave","year":"2004","journal-title":"Methods Mol Biol"},{"issue":"09","key":"ref21","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1182\/blood-2007-03-080184","article-title":"Megakaryocyte-restricted MYH9 inactivation dramatically affects hemostasis while preserving platelet aggregation and secretion","volume":"110","author":"C L\u00e9on","year":"2007","journal-title":"Blood"},{"issue":"02","key":"ref22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1101\/cshperspect.a005132","article-title":"Extracellular matrix proteins in hemostasis and thrombosis","volume":"4","author":"W Bergmeier","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"07","key":"ref23","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1182\/blood-2006-02-002063","article-title":"Impact of fibronectin assembly on platelet thrombus formation in response to type I collagen and von Willebrand factor","volume":"108","author":"J Cho","year":"2006","journal-title":"Blood"},{"issue":"06","key":"ref24","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1161\/01.ATV.0000216282.58291.c6","article-title":"Decreased plasma fibronectin leads to delayed thrombus growth in injured arterioles","volume":"26","author":"J Matuskova","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"05","key":"ref25","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1073\/pnas.2628067100","article-title":"Plasma fibronectin promotes thrombus growth and stability in injured arterioles","volume":"100","author":"H Ni","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"03","key":"ref26","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1172\/JCI9896","article-title":"Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen","volume":"106","author":"H Ni","year":"2000","journal-title":"J Clin Invest"},{"issue":"01","key":"ref27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1182\/blood.V98.1.117","article-title":"Assembly of a fibronectin matrix by adherent platelets stimulated by lysophosphatidic acid and other agonists","volume":"98","author":"O E Olorundare","year":"2001","journal-title":"Blood"},{"issue":"08","key":"ref28","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1074\/jbc.M608342200","article-title":"CD40 ligand binds to alpha5beta1 integrin and triggers cell signaling","volume":"282","author":"C L\u00e9veill\u00e9","year":"2007","journal-title":"J Biol Chem"},{"issue":"06","key":"ref29","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1161\/ATVBAHA.114.305127","article-title":"Platelet CD40L modulates thrombus growth via phosphatidylinositol 3-kinase \u03b2, and not via CD40 and I\u03baB kinase \u03b1","volume":"35","author":"M JE Kuijpers","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"15","key":"ref30","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1182\/blood-2013-06-508721","article-title":"\u03b21 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse","volume":"122","author":"T Petzold","year":"2013","journal-title":"Blood"},{"issue":"02","key":"ref31","first-page":"908","article-title":"Platelet ITAM signaling is critical for vascular integrity in inflammation","volume":"123","author":"Y Boulaftali","year":"2013","journal-title":"J Clin Invest"},{"issue":"08","key":"ref32","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1182\/blood-2014-12-617159","article-title":"Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex-mediated inflammation in mice","volume":"126","author":"A Gros","year":"2015","journal-title":"Blood"},{"issue":"06","key":"ref33","doi-asserted-by":"crossref","first-page":"e256","DOI":"10.3324\/haematol.2017.182162","article-title":"The contribution of platelet glycoprotein receptors to inflammatory bleeding prevention is stimulus and organ dependent","volume":"103","author":"J Rayes","year":"2018","journal-title":"Haematologica"},{"issue":"05","key":"ref34","first-page":"1072","article-title":"Role of murine integrin alpha2beta1 in thrombus stabilization and embolization: contribution of thromboxane A2","volume":"98","author":"M JE Kuijpers","year":"2007","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref35","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.yjmcc.2010.04.009","article-title":"Impact of glycoprotein VI and platelet adhesion on atherosclerosis\u2013a possible role of fibronectin","volume":"49","author":"A B\u00fcltmann","year":"2010","journal-title":"J Mol Cell Cardiol"},{"issue":"12","key":"ref36","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1161\/01.RES.0000150373.15149.ff","article-title":"Molecular imaging of atherosclerotic plaques using a human antibody against the extra-domain B of fibronectin","volume":"95","author":"C M Matter","year":"2004","journal-title":"Circ Res"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1659-6214.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T14:46:50Z","timestamp":1660142810000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1659-6214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":36,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2022,6,14]]},"published-print":{"date-parts":[[2022,5]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1659-6214","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,1]]},"published":{"date-parts":[[2021,10,1]]}}}