{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:48:11Z","timestamp":1787806091706,"version":"build-2784847793"},"reference-count":59,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Beta-2 Glycoprotein I (\u03b22-GPI) is the main target of anti-phospholipid antibodies (aPL) in the autoimmune anti-phospholipid syndrome, characterized by increased risk of stroke. We here investigated the antibody independent role of \u03b22-GPI after ischemia\/reperfusion, modeled in vivo by transient middle cerebral artery occlusion (tMCAo) in male C57Bl\/6J mice; in vitro by subjecting immortalized human brain microvascular endothelial cells (ihBMEC) to 16\u2009h hypoxia and 4\u2009h re-oxygenation. ApoH (coding for \u03b22-GPI) was upregulated selectively in the liver at 48\u2009h after tMCAo. At the same time \u03b22-GPI circulating levels increased. \u03b22-GPI was detectable in brain parenchyma and endothelium at all time points after tMCAo. Parenchymal \u03b22-GPI recognized apoptotic neurons (positive for annexin V, C3 and TUNEL) cleared by CD68+ brain macrophages. Hypoxic ihBMEC showed increased release of IL-6, over-expression of thrombomodulin and IL-1\u03b1 after re-oxygenation with \u03b22-GPI alone. \u03b22-GPI interacted with mannose-binding lectin in mouse plasma and ihBMEC medium, potentially involved in formation of thrombi. We show for the first time that brain ischemia triggers the hepatic production of \u03b22-GPI. \u03b22-GPI is present in the ischemic endothelium, enhancing vascular inflammation, and extravasates binding stressed neurons before their clearance by phagocytosis. Thus \u03b22-GPI may be a new mediator of brain injury following ischemic stroke.<\/jats:p>","DOI":"10.1177\/0271678x20984551","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T22:29:03Z","timestamp":1610663343000},"page":"2038-2053","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["\u03b22 glycoprotein I participates in phagocytosis of apoptotic neurons and in vascular injury in experimental brain stroke"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-2472","authenticated-orcid":false,"given":"Claudia","family":"Grossi","sequence":"first","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Laboratory of Immuno-Rheumatology, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Artusi","sequence":"additional","affiliation":[{"name":"Rheumatology Department, ASST Gaetano Pini-CTO, Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PierLuigi","family":"Meroni","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Laboratory of Immuno-Rheumatology, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8967-9678","authenticated-orcid":false,"given":"Maria Orietta","family":"Borghi","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Laboratory of Immuno-Rheumatology, Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Neglia","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Department of Neuroscience, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Adele","family":"Lonati","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Laboratory of Immuno-Rheumatology, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Oggioni","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Department of Neuroscience, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Tedesco","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Laboratory of Immuno-Rheumatology, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-0003","authenticated-orcid":false,"given":"Maria-Grazia","family":"De Simoni","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Department of Neuroscience, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Department of Neuroscience, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"bibr1-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.011238"},{"key":"bibr2-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(17)30066-X"},{"key":"bibr3-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0032-6"},{"key":"bibr4-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.01753.x"},{"key":"bibr5-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-010-0144-8"},{"key":"bibr6-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04327.x"},{"key":"bibr7-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-007-8055-9"},{"key":"bibr8-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/239398"},{"key":"bibr9-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.100610"},{"key":"bibr10-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704990200"},{"key":"bibr11-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00773"},{"key":"bibr12-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-672139"},{"key":"bibr13-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000570"},{"key":"bibr14-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19874509"},{"key":"bibr15-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.004111"},{"key":"bibr16-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.311058"},{"key":"bibr17-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-537704"},{"key":"bibr18-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17709185"},{"key":"bibr19-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63744-3"},{"key":"bibr20-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.103051"},{"key":"bibr21-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-174"},{"key":"bibr22-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1002\/art.30383"},{"key":"bibr23-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1038\/srep15915"},{"key":"bibr24-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"key":"bibr25-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0821-11.2011"},{"key":"bibr26-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"bibr27-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00288"},{"key":"bibr28-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0277-y"},{"key":"bibr29-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-333617"},{"key":"bibr30-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1002\/art.39187"},{"key":"bibr31-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2015.4041"},{"key":"bibr32-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008433"},{"key":"bibr33-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00380"},{"key":"bibr34-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0225-1"},{"key":"bibr35-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1401-z"},{"key":"bibr36-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186513"},{"key":"bibr37-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-215335"},{"key":"bibr38-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1002\/art.10187"},{"key":"bibr39-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204838"},{"key":"bibr40-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2014.06.005"},{"key":"bibr41-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2004.07.017"},{"key":"bibr42-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1002\/art.30633"},{"key":"bibr43-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-339564"},{"key":"bibr44-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0684-6"},{"key":"bibr45-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00081"},{"key":"bibr46-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.012407"},{"key":"bibr47-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-017-0562-2"},{"key":"bibr48-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.5.2610"},{"key":"bibr49-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1007\/BF00303252"},{"key":"bibr50-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000078322.96027.78"},{"key":"bibr51-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.05.014"},{"key":"bibr52-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.04.019"},{"key":"bibr53-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.4679"},{"key":"bibr54-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws075"},{"key":"bibr55-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1002\/art.21009"},{"key":"bibr56-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-017-0555-x"},{"key":"bibr57-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1177\/1076029611432744"},{"key":"bibr58-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-376038"},{"key":"bibr59-0271678X20984551","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.11.012"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X20984551","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X20984551","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X20984551","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:13:15Z","timestamp":1777493595000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X20984551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,14]]},"references-count":59,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1177\/0271678X20984551"],"URL":"https:\/\/doi.org\/10.1177\/0271678x20984551","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,14]]}}}