{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:37:57Z","timestamp":1784266677962,"version":"3.55.0"},"reference-count":78,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"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":["Circulation Research"],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Receptors that bind antibodies are essential for protective adaptive immune responses against antibody-opsonized pathogens, yet their engagement by antibody-autoantigen complexes can drive chronic inflammation in autoimmune diseases. Megakaryocytes, the precursor cells of platelets, express such receptors. However, their response to immunoglobulin G antibodies remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We used both systemic lupus erythematosus and COVID-19 as relevant examples of autoimmune and infection-driven contexts in which antibodies are involved to characterize human and mouse megakaryocyte responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We found that megakaryocytes internalized immune complexes composed of autoantigens or SARS-CoV-2. In both human and mouse megakaryocytes, immune complexes triggered the release of chemokines and procoagulant extracellular vesicles. This process required Fc\u03b3RIIA (Fc gamma receptor IIA) engagement, downstream Syk (spleen tyrosine kinase) signaling, and protein translation. A detailed analysis revealed that megakaryocyte-derived extracellular vesicles did not contain organelles and were largely indistinguishable from a subset of small-sized extracellular vesicles released by activated platelets. In Fc\u03b3RIIA-transgenic mice, we analyzed megakaryocytes in both the bone marrow and lungs in a lupus model, whereas megakaryocytes were examined in the lungs in a COVID-19 model. In all cases, immunoglobulins were detected in close proximity to Fc\u03b3RIIA-expressing megakaryocytes. Notably, the chemokine CXCL2 (C-X-C motif ligand-2) was increased in Fc\u03b3RIIA-expressing mice under disease conditions. Tissue spatial analysis revealed that CXCL2 predominantly localized to megakaryocytes, supporting these cells as a major source. Furthermore, SARS-CoV-2 stimulated megakaryocytes to release CXCL2 only in the presence of IgG from SARS-CoV-2 immune individuals, and this response was strictly dependent on Fc\u03b3RIIA expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings suggest that megakaryocytes contribute to adaptive immune responses through Fc\u03b3RIIA-mediated signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.327999","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:01:00Z","timestamp":1781600460000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Megakaryocytes Internalize and Are Activated by Immune Complexes"],"prefix":"10.1161","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5699-6626","authenticated-orcid":true,"given":"Florian","family":"Puhm","sequence":"first","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Axe Maladies Infectieuses et Immunitaires du Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval, Canada (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4697-046X","authenticated-orcid":true,"given":"Isabelle","family":"Allaeys","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Axe Maladies Infectieuses et Immunitaires du Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval, Canada (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4921-8687","authenticated-orcid":true,"given":"Eleonora","family":"Petito","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Italy (E.P., L.B., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5147-989X","authenticated-orcid":true,"given":"Yaqiu","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and University North Carolina (UNC) Blood Research Center, University of North Carolina at Chapel Hill (Y. Sang, A.S.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Tupin","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Axe Maladies Infectieuses et Immunitaires du Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval, Canada (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9724-4164","authenticated-orcid":true,"given":"Ana","family":"dos Santos Pereira Andrade","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Axe Maladies Infectieuses et Immunitaires du Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval, Canada (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-5012","authenticated-orcid":true,"given":"Etienne","family":"Dor\u00e9","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Axe Maladies Infectieuses et Immunitaires du Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval, Canada (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-1980","authenticated-orcid":true,"given":"Isabelle","family":"Dubuc","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Axe Maladies Infectieuses et Immunitaires du Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval, Canada (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Vaillancourt","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Axe Maladies Infectieuses et Immunitaires du Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval, Canada (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9300-4232","authenticated-orcid":true,"given":"M\u00e9lanie","family":"Dieud\u00e9","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Qu\u00e9bec City, Qu\u00e9bec, Canada (M.D., M.-J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6234-682X","authenticated-orcid":true,"given":"Marie-Jos\u00e9e","family":"H\u00e9bert","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Qu\u00e9bec City, Qu\u00e9bec, Canada (M.D., M.-J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7114-2266","authenticated-orcid":true,"given":"Bogdan I.","family":"Florea","sequence":"additional","affiliation":[{"name":"Gorlaeus Laboratories, Leiden Institute of Chemistry and Netherlands Proteomics Centre (B.I.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-6230","authenticated-orcid":true,"given":"Patrick","family":"Tr\u00e9panier","sequence":"additional","affiliation":[{"name":"H\u00e9ma-Qu\u00e9bec, Affaires M\u00e9dicales et Innovation, Qu\u00e9bec City, Qu\u00e9bec, Canada (P.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-1822","authenticated-orcid":true,"given":"Valance A.","family":"Washington","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Oakland University, Rochester, MI (V.A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotis","family":"Senis","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Nutrition Research, Institut National de la Sant\u00e9 et de la Recherche 1263, Faculty of Medicine, Aix-Marseille University, France (Y. Senis)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7278-2596","authenticated-orcid":true,"given":"Paul R.","family":"Fortin","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Axe Maladies Infectieuses et Immunitaires du Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec-Universit\u00e9 Laval, Canada (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-352X","authenticated-orcid":true,"given":"Alain R.","family":"Brisson","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche-Chimie et Biologie des Membranes et des Nano-objets (UMR-CBMN), Universit\u00e9 de Bordeaux, Centre National de la Recherche Scientifique (CNRS), Institut Polytechnique de Bordeaux (IPB), Pessac, France (A.R.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2845-2303","authenticated-orcid":true,"given":"Alisa S.","family":"Wolberg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and University North Carolina (UNC) Blood Research Center, University of North Carolina at Chapel Hill (Y. Sang, A.S.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0333-0948","authenticated-orcid":true,"given":"Loredana","family":"Bury","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Italy (E.P., L.B., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5010-4586","authenticated-orcid":true,"given":"Louis","family":"Flamand","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada."},{"name":"Centre de Recherche ARThrite\u2013Arthrite, Recherche, Traitements (F.P., I.A., F.T., A.d.S.P.A., E.D., I.D., M.V., P.R.F., L.F., E.B.), Universit\u00e9 Laval, Qu\u00e9bec 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