{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:32:23Z","timestamp":1790821943026,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Although most plasma FVIII (Factor VIII) circulates in complex with VWF (von Willebrand factor), a minority (3%\u20135%) circulates as free-FVIII, which is rapidly cleared. Consequently, 20% of total FVIII may be cleared as free-FVIII. Critically, the mechanisms of free-FVIII clearance remain poorly understood. However, recent studies have implicated the MGL (macrophage galactose lectin) in modulating VWF clearance.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Since VWF and FVIII share similar glycosylation, we investigated the role of MGL in FVIII clearance. FVIII binding to MGL was assessed in immunosorbent and cell-based assays. In vivo, FVIII clearance was assessed in\n              <jats:italic>\n                MGL1\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              and\n              <jats:italic>\n                VWF\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              <jats:italic>\n                \/FVIII\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              In vitro\u2013binding studies identified MGL as a novel macrophage receptor that binds free-FVIII in a glycan-dependent manner.\n              <jats:italic>\n                MGL1\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              and\n              <jats:italic>\n                MGL1\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              mice who received an anti-MGL1\/2 blocking antibody both showed significantly increased endogenous FVIII activity compared with wild-type mice (\n              <jats:italic>P<\/jats:italic>\n              =0.036 and\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001, respectively). MGL inhibition also prolonged the half-life of infused FVIII in\n              <jats:italic>\n                FVIII\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              mice. To assess whether MGL plays a role in the clearance of free FVIII in a VWF-independent manner, in vivo clearance experiments were repeated in dual\n              <jats:italic>\n                VWF\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              <jats:italic>\n                \/FVIII\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              mice. Importantly, the rapid clearance of free FVIII in\n              <jats:italic>\n                VWF\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              <jats:italic>\n                \/FVIII\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              mice was significantly (\n              <jats:italic>P<\/jats:italic>\n              =0.012) prolonged in the presence of anti-MGL1\/2 antibodies. Finally, endogenous plasma FVIII levels in\n              <jats:italic>\n                VWF\n                <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <\/jats:italic>\n              mice were significantly increased following MGL inhibition (\n              <jats:italic>P<\/jats:italic>\n              =0.016).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Cumulatively, these findings demonstrate that MGL plays an important role in regulating macrophage-mediated clearance of both VWF-bound FVIII and free-FVIII in vivo. We propose that this novel FVIII clearance pathway may be of particular clinical importance in patients with type 2N or type 3 Von Willebrand disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.317807","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T10:00:55Z","timestamp":1675332055000},"page":"540-546","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Macrophage Galactose Lectin Contributes to the Regulation of FVIII (Factor VIII) Clearance in Mice\u2014Brief Report"],"prefix":"10.1161","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1730-8485","authenticated-orcid":true,"given":"Soracha E.","family":"Ward","sequence":"first","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Guest","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-0644","authenticated-orcid":true,"given":"Ciara","family":"Byrne","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-5354","authenticated-orcid":true,"given":"Patricia","family":"Lopes","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie M.","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dearbhla","family":"Doherty","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Science (D.O.), University College Dublin, Ireland."},{"name":"BEACON Bioeconomy Research Centre (D.O.), University College Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gutierrez Llaneza","sequence":"additional","affiliation":[{"name":"Biomedical Research Facility, Royal College of Surgeons, Dublin, Ireland (S.G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Chion","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judicael","family":"Fazavana","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-7293","authenticated-orcid":true,"given":"Padraic G.","family":"Fallon","sequence":"additional","affiliation":[{"name":"Inflammation and Immunity Research Group, Trinity Translational Medicine Institute, St James\u2019s Hospital, Trinity College Dublin, Ireland (P.G.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J.S.","family":"Preston","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."},{"name":"National Children\u2019s Research Centre, Our Lady\u2019s Children\u2019s Hospital, Dublin, Ireland (R.J.S.P., J.S.O)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Bloodworks Research Institute, Seattle, WA (J.M.J.)."},{"name":"Department of Medicine, University of Washington, Seattle (J.M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2558-2089","authenticated-orcid":true,"given":"Steven W.","family":"Pipe","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor (S.W.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Turecek","sequence":"additional","affiliation":[{"name":"Baxalta Innovations GmbH, A Member of the Takeda Group of Companies, Vienna, Austria (P.L.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0309-3313","authenticated-orcid":true,"given":"James S.","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland (S.E.W., T.G., C.B., P.L., J.M.O., D.D., A.C., J.F., R.J.S.P., J.S.O.)."},{"name":"National Children\u2019s Research Centre, Our Lady\u2019s Children\u2019s Hospital, Dublin, Ireland (R.J.S.P., J.S.O)."},{"name":"National Centre for Coagulation Disorders, St James\u2019s Hospital, Dublin, Ireland (J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the iPATH Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-713289"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v85.11.3150.bloodjournal85113150"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14078"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi300232d"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14404"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02572.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02320.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14204"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.09.011"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1532\/ijh97.05113"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01389.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.115.306915"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.063297"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515464112"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14471"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-787853"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.274720"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190723"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13537"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-709436"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m310436200"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12875"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12885"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-303727"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-133181"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m203774200"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m110.113613"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15565"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v95.5.1703.005k20_1703_1708"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.122.317807","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:33:39Z","timestamp":1715556819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.122.317807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1161\/ATVBAHA.122.317807"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.122.317807","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"2022-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}