{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:32:06Z","timestamp":1787063526036,"version":"build-2736575974"},"reference-count":136,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T00:00:00Z","timestamp":1555027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CISI Lab Project Regione Campania","award":["No Number is Available"],"award-info":[{"award-number":["No Number is Available"]}]},{"name":"CR\u00e9ME and TIMING Projects Regione Campania","award":["No Number is Available"],"award-info":[{"award-number":["No Number is Available"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>B cell superantigens, also called immunoglobulin superantigens, bind to the variable regions of either the heavy or light chain of immunoglobulins mirroring the lymphocyte-activating properties of classical T cell superantigens. Protein A of Staphylococcus aureus, protein L of Peptostreptococcus magnus, and gp120 of HIV are typical immunoglobulin superantigens. Mast cells are immune cells expressing the high-affinity receptor for IgE (Fc\u03b5RI) and are strategically located in the human heart, where they play a role in several cardiometabolic diseases. Here, we investigated whether immunoglobulin superantigens induced the activation of human heart mast cells (HHMCs). Protein A induced the de novo synthesis of cysteinyl leukotriene C4 (LTC4) from HHMCs through the interaction with IgE VH3+ bound to Fc\u03b5RI. Protein L stimulated the production of prostaglandin D2 (PGD2) from HHMCs through the interaction with \u03ba light chains of IgE. HIV glycoprotein gp120 induced the release of preformed (histamine) and de novo synthesized mediators, such as cysteinyl leukotriene C4 (LTC4), angiogenic (VEGF-A), and lymphangiogenic (VEGF-C) factors by interacting with the VH3 region of IgE. Collectively, our data indicate that bacterial and viral immunoglobulin superantigens can interact with different regions of IgE bound to Fc\u03b5RI to induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from human cardiac mast cells.<\/jats:p>","DOI":"10.3390\/ijms20081828","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T12:55:04Z","timestamp":1555073704000},"page":"1828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Superantigenic Activation of Human Cardiac Mast Cells"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-4657","authenticated-orcid":false,"given":"Gilda","family":"Varricchi","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), 80100 Naples, Italy"},{"name":"World Allergy Organization (WAO) Center of Excellence, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Loffredo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), 80100 Naples, Italy"},{"name":"World Allergy Organization (WAO) Center of Excellence, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Borriello","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), 80100 Naples, Italy"},{"name":"World Allergy Organization (WAO) Center of Excellence, 80100 Naples, Italy"},{"name":"Division of Gastroenterology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pecoraro","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-7521","authenticated-orcid":false,"given":"Felice","family":"Rivellese","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), 80100 Naples, Italy"},{"name":"World Allergy Organization (WAO) Center of Excellence, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Spadaro","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), 80100 Naples, Italy"},{"name":"World Allergy Organization (WAO) Center of Excellence, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9849-4701","authenticated-orcid":false,"given":"Gianni","family":"Marone","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), 80100 Naples, Italy"},{"name":"World Allergy Organization (WAO) Center of Excellence, 80100 Naples, Italy"},{"name":"Institute of Experimental Endocrinology and Oncology \u201cGaetano Salvatore\u201d, National Research Council (CNR), 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0092-8674(89)90980-X","article-title":"The V beta-specific superantigen staphylococcal enterotoxin B: Stimulation of mature T cells and clonal deletion in neonatal mice","volume":"56","author":"White","year":"1989","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0065-2776(08)60534-9","article-title":"Superantigens and their potential role in human disease","volume":"54","author":"Kotzin","year":"1993","journal-title":"Adv. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Marone, G. (2007). Superantigens and superallergens. Chem. Immunol. Allergy, 93.","DOI":"10.1159\/isbn.978-3-318-01451-8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1126\/science.2185544","article-title":"The staphylococcal enterotoxins and their relatives","volume":"248","author":"Marrack","year":"1990","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.4049\/jimmunol.145.4.1176","article-title":"Protein F. A novel F(ab)-binding factor, present in normal liver, and largely released in the digestive tract during hepatitis","volume":"145","author":"Bouvet","year":"1990","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/353605a0","article-title":"Antigen presentation. The second class story","volume":"353","author":"Germain","year":"1991","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1126\/science.270.5243.1821","article-title":"Crystal structure of the V alpha domain of a T cell antigen receptor","volume":"270","author":"Fields","year":"1995","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S1074-7613(00)80646-9","article-title":"Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B","volume":"9","author":"Li","year":"1998","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1084\/jem.182.6.1833","article-title":"Superantigen binding to a T cell receptor beta chain of known three-dimensional structure","volume":"182","author":"Malchiodi","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0969-2126(02)00759-1","article-title":"Structures of two streptococcal superantigens bound to TCR beta chains reveal diversity in the architecture of T cell signaling complexes","volume":"10","author":"Sundberg","year":"2002","journal-title":"Structure"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s00281-004-0190-2","article-title":"B cell superantigens: A microbe\u2019s answer to innate-like B cells and natural antibodies","volume":"26","author":"Goodyear","year":"2005","journal-title":"Springer Semin. Immunopathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.clim.2004.08.019","article-title":"B-lymphocytes, innate immunity, and autoimmunity","volume":"114","author":"Viau","year":"2005","journal-title":"Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1159\/000100897","article-title":"Role of staphylococcal superantigens in airway disease","volume":"93","author":"Bachert","year":"2007","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1159\/000100896","article-title":"Role of superallergens in allergic disorders","volume":"93","author":"Marone","year":"2007","journal-title":"Chem. Immunol. Allergy."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1398-9995.2010.02502.x","article-title":"Staphylococci and staphylococcal superantigens in asthma and rhinitis: A systematic review and meta-analysis","volume":"66","author":"Pastacaldi","year":"2011","journal-title":"Allergy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0960-9822(91)90097-G","article-title":"B-cell superantigens?","volume":"1","author":"Pascual","year":"1991","journal-title":"Curr. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/clim.2001.5143","article-title":"A model B-cell superantigen and the immunobiology of B lymphocytes","volume":"102","author":"Silverman","year":"2002","journal-title":"Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0167-5699(95)80009-3","article-title":"B-cell superantigens: Implications for selection of the human antibody repertoire","volume":"16","author":"Zouali","year":"1995","journal-title":"Immunol. Today"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1159\/000100856","article-title":"Diversity in Staphylococcus aureus enterotoxins","volume":"93","author":"Thomas","year":"2007","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nature01962","article-title":"Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation","volume":"425","author":"Friedrich","year":"2003","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"Lowy","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1073\/pnas.1317181111","article-title":"Release of protein A from the cell wall of Staphylococcus aureus","volume":"111","author":"Becker","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"822","DOI":"10.4049\/jimmunol.97.6.822","article-title":"\u201cProtein A\u201d from S. aureus. I. Pseudo-immune reaction with human gamma-globulin","volume":"97","author":"Forsgren","year":"1966","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1365-3083.1981.tb00143.x","article-title":"Comparison of mechanisms of interaction between protein A from Staphylococcus aureus and human monoclonal IgG, IgA and IgM in relation to the classical FC gamma and the alternative F(ab\u2019)2 epsilon protein A interactions","volume":"13","year":"1981","journal-title":"Scand. J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1097\/00002030-200005260-00004","article-title":"The immunoglobulin superantigen-binding site of HIV-1 gp120 activates human basophils","volume":"14","author":"Florio","year":"2000","journal-title":"AIDS"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"589","DOI":"10.4049\/jimmunol.164.2.589","article-title":"HIV-1 gp120 induces IL-4 and IL-13 release from human Fc epsilon RI+ cells through interaction with the VH3 region of IgE","volume":"164","author":"Patella","year":"2000","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.amjsurg.2016.05.018","article-title":"Characteristics and treatment of human epidermal growth factor receptor 2 positive breast cancer: 43,485 cases from the National Cancer Database treated in 2010 and 2011","volume":"213","author":"Killelea","year":"2017","journal-title":"Am. J. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/31405","article-title":"Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody","volume":"393","author":"Kwong","year":"1998","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1126\/science.272.5263.872","article-title":"HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor","volume":"272","author":"Feng","year":"1996","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/381667a0","article-title":"HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5","volume":"381","author":"Dragic","year":"1996","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1073\/pnas.94.4.1356","article-title":"Identification of the B cell superantigen-binding site of HIV-1 gp120","volume":"94","author":"Karray","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0167-5699(97)01101-8","article-title":"B-cell superantigens","volume":"18","author":"Silverman","year":"1997","journal-title":"Immunol. Today."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000100860","article-title":"B cell superantigens subvert innate functions of B cells","volume":"93","author":"Zouali","year":"2007","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Durand, M., Chartrand-Lefebvre, C., Baril, J.G., Trottier, S., Trottier, B., Harris, M., Walmsley, S., Conway, B., Wong, A., and Routy, J.P. (2017). The Canadian HIV and aging cohort study\u2014Determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2692-2"},{"key":"ref_35","first-page":"74","article-title":"HIV and cardiovascular disease: Role of immunometabolic perturbations","volume":"33","author":"Teer","year":"2018","journal-title":"Physiology (Bethesda)"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/19420862.2015.1116657","article-title":"A method to confer Protein L binding ability to any antibody fragment","volume":"8","author":"Lakhrif","year":"2016","journal-title":"mAbs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.4049\/jimmunol.140.4.1194","article-title":"Protein L. A novel bacterial cell wall protein with affinity for Ig L chains","volume":"140","author":"Bjorck","year":"1988","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/0161-5890(85)90073-2","article-title":"A non-immune interaction between the light chain of human immunoglobulin and a surface component of a Peptococcus magnus strain","volume":"22","author":"Myhre","year":"1985","journal-title":"Mol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.4049\/jimmunol.145.9.3054","article-title":"Protein L. A bacterial Ig-binding protein that activates human basophils and mast cells","volume":"145","author":"Patella","year":"1990","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.1128\/IAI.68.10.5517-5524.2000","article-title":"Bacterial immunoglobulin superantigen proteins A and L activate human heart mast cells by interacting with immunoglobulin E","volume":"68","author":"Genovese","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.4049\/jimmunol.170.4.1854","article-title":"Immunoglobulin superantigen protein L induces IL-4 and IL-13 secretion from human Fc epsilon RI+ cells through interaction with the kappa light chains of IgE","volume":"170","author":"Genovese","year":"2003","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1016\/S0021-9258(18)45867-X","article-title":"Protein L from Peptostreptococcus magnus binds to the kappa light chain variable domain","volume":"267","author":"Nilson","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.molimm.2018.11.009","article-title":"Distribution of mast cells within the mouse heart and its dependency on Mitf","volume":"105","author":"Ingason","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ajpath.2013.10.016","article-title":"IgE receptor-mediated mast-cell renin release","volume":"184","author":"Aldi","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1161\/CIRCRESAHA.117.311185","article-title":"Mast cells granular contents are crucial for deep vein thrombosis in mice","volume":"121","author":"Ponomaryov","year":"2017","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/path.1690","article-title":"Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts","volume":"205","author":"Somasundaram","year":"2005","journal-title":"J. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.4049\/jimmunol.165.5.2798","article-title":"IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury","volume":"165","author":"Frangogiannis","year":"2000","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.4049\/jimmunol.154.6.2855","article-title":"Human heart mast cells. Isolation, purification, ultrastructure, and immunologic characterization","volume":"154","author":"Patella","year":"1995","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.4049\/jimmunol.157.3.1219","article-title":"Eosinophil granule proteins activate human heart mast cells","volume":"157","author":"Patella","year":"1996","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0021-9150(95)05794-3","article-title":"Mast cells accompany microvessels in human coronary atheromas: Implications for intimal neovascularization and hemorrhage","volume":"123","author":"Kaartinen","year":"1996","journal-title":"Atherosclerosis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1161\/01.CIR.91.2.275","article-title":"Increase and redistribution of cardiac mast cells in auricular thrombosis. Possible role of kit ligand","volume":"91","author":"Bankl","year":"1995","journal-title":"Circulation"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12627","article-title":"Human mast cells and basophils-How are they similar how are they different?","volume":"282","author":"Varricchi","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.coph.2014.07.002","article-title":"Immunopharmacological modulation of mast cells","volume":"17","author":"Borriello","year":"2014","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/imr.12634","article-title":"Mast cells as sources of cytokines, chemokines, and growth factors","volume":"282","author":"Mukai","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.ajpath.2015.07.025","article-title":"The mast cell-IgE paradox: From homeostasis to anaphylaxis","volume":"186","author":"Galli","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/cea.12675","article-title":"Mast cells in asthma\u2014State of the art","volume":"46","author":"Bradding","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jaci.2018.01.034","article-title":"Mast cells signal their importance in health and disease","volume":"142","author":"Olivera","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/imr.12623","article-title":"The contribution of mast cells to bacterial and fungal infection immunity","volume":"282","author":"Piliponsky","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000452889","article-title":"Are basophils and mast cells masters in HIV Infection?","volume":"171","author":"Marone","year":"2016","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1136\/annrheumdis-2014-205562","article-title":"Toll-like receptor triggering augments activation of human mast cells by anti-citrullinated protein antibodies","volume":"74","author":"Suurmond","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.jaci.2009.01.044","article-title":"Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects","volume":"123","author":"Detoraki","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.coi.2018.05.002","article-title":"Innate effector cells in angiogenesis and lymphangiogenesis","volume":"53","author":"Varricchi","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ejphar.2015.03.088","article-title":"Mast cells and basophils in inflammatory and tumor angiogenesis and lymphangiogenesis","volume":"778","author":"Marone","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.4049\/jimmunol.172.2.1227","article-title":"Prostaglandin E2 induces degranulation-independent production of vascular endothelial growth factor by human mast cells","volume":"172","author":"Marshall","year":"2004","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1073\/pnas.1000803107","article-title":"IL-33 augments substance P-induced VEGF secretion from human mast cells and is increased in psoriatic skin","volume":"107","author":"Theoharides","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jaad.2015.03.041","article-title":"Angiogenesis and lymphangiogenesis in inflammatory skin disorders","volume":"73","author":"Varricchi","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1002\/art.39192","article-title":"Ability of interleukin-33- and immune complex-triggered activation of human mast cells to down-regulate monocyte-mediated immune responses","volume":"67","author":"Rivellese","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.autrev.2017.04.001","article-title":"Mast cells in rheumatoid arthritis: friends or foes?","volume":"16","author":"Rivellese","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1136\/annrheumdis-2018-213418","article-title":"Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production","volume":"77","author":"Rivellese","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5175","DOI":"10.1038\/onc.2014.441","article-title":"Mast cells induce epithelial-to-mesenchymal transition and stem cell features in human thyroid cancer cells through an IL-8-Akt-Slug pathway","volume":"34","author":"Visciano","year":"2015","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1168556","DOI":"10.1080\/2162402X.2016.1168556","article-title":"The immune network in thyroid cancer","volume":"5","author":"Galdiero","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3389\/fimmu.2017.00424","article-title":"Are mast cells MASTers in cancer?","volume":"8","author":"Varricchi","year":"2017","journal-title":"Front Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/exd.13107","article-title":"Controversial role of mast cells in skin cancers","volume":"26","author":"Varricchi","year":"2017","journal-title":"Exp. Dermatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/0891693042000196200","article-title":"Mast cells and innate cytokines are associated with susceptibility to autoimmune heart disease following coxsackievirus B3 infection","volume":"37","author":"Fairweather","year":"2004","journal-title":"Autoimmunity"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1161\/CIRCULATIONAHA.117.029626","article-title":"Cardiac toxicity of immune checkpoint inhibitors: Cardio-oncology meets immunology","volume":"136","author":"Varricchi","year":"2017","journal-title":"Circulation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1084\/jem.20160081","article-title":"Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction","volume":"213","author":"Ngkelo","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1161\/01.CIR.97.10.971","article-title":"Stem cell factor in mast cells and increased mast cell density in idiopathic and ischemic cardiomyopathy","volume":"97","author":"Patella","year":"1998","journal-title":"Circulation"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/nrcardio.2015.117","article-title":"Mast cells in human and experimental cardiometabolic diseases","volume":"12","author":"Shi","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7322","DOI":"10.4049\/jimmunol.177.10.7322","article-title":"Expression and functions of the vascular endothelial growth factors and their receptors in human basophils","volume":"177","author":"Prevete","year":"2006","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5232","DOI":"10.4049\/jimmunol.0902501","article-title":"Production of vascular endothelial growth factors from human lung macrophages induced by group IIA and group X secreted phospholipases A2","volume":"184","author":"Granata","year":"2010","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1189\/jlb.3HI1214-584R","article-title":"Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors","volume":"99","author":"Staiano","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3389\/fimmu.2017.00443","article-title":"Group V secreted phospholipase A2 induces the release of proangiogenic and antiangiogenic factors by human neutrophils","volume":"8","author":"Loffredo","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"861","DOI":"10.4049\/jimmunol.138.3.861","article-title":"Human skin mast cells: Their dispersion, purification, and secretory characterization","volume":"138","author":"Benyon","year":"1987","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jneuroim.2005.02.015","article-title":"Evidence for a restricted rather than generalized stimulatory response of skin-derived human mast cells to substance P","volume":"163","author":"Guhl","year":"2005","journal-title":"J. Neuroimmunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/art.1780390723","article-title":"Human synovial mast cells. I. Ultrastructural in situ and in vitro immunologic characterization","volume":"39","author":"Marino","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/1523-1747.ep12277582","article-title":"IgG anti-IgE from atopic dermatitis induces mediator release from basophils and mast cells","volume":"93","author":"Marone","year":"1989","journal-title":"J. Investig. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrcardio.2013.94","article-title":"Vascular endothelial growth factor in heart failure","volume":"10","author":"Taimeh","year":"2013","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1111\/all.12878","article-title":"T follicular helper (Tfh) cells in normal immune responses and in allergic disorders","volume":"71","author":"Varricchi","year":"2016","journal-title":"Allergy"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1172\/JCI46028","article-title":"IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe-\/-mice","volume":"121","author":"Wang","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1161\/01.CIR.77.6.1245","article-title":"Serum immunoglobulin E response to myocardial infarction","volume":"77","author":"Szczeklik","year":"1988","journal-title":"Circulation"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1001\/archinte.158.13.1434","article-title":"Prediction of myocardial infarction in dyslipidemic men by elevated levels of immunoglobulin classes A, E, and G, but not M","volume":"158","author":"Kovanen","year":"1998","journal-title":"Arch. Intern. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1194\/jlr.M077503","article-title":"Chymase released from hypoxia-activated cardiac mast cells cleaves human apoA-I at Tyr(192) and compromises its cardioprotective activity","volume":"59","author":"Kareinen","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.tips.2011.05.005","article-title":"Mast cells squeeze the heart and stretch the gird: their role in atherosclerosis and obesity","volume":"32","author":"Theoharides","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1161\/CIRCRESAHA.117.310978","article-title":"Multifunctional role of chymase in acute and chronic tissue injury and remodeling","volume":"122","author":"Collawn","year":"2018","journal-title":"Circ. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1111\/jce.12995","article-title":"Mast cells play an important role in the pathogenesis of hyperglycemia-induced atrial fibrillation","volume":"27","author":"Uemura","year":"2016","journal-title":"J Cardiovasc. Electrophysiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jaci.2016.03.051","article-title":"Proteome analysis of mast cell releasates reveals a role for chymase in the regulation of coagulation factor XIIIA levels via proteolytic degradation","volume":"139","author":"Shubin","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41467-017-00327-8","article-title":"Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B","volume":"8","author":"Wroblewski","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"840","DOI":"10.3389\/fimmu.2017.00840","article-title":"Mast cell coupling to the kallikrein-kinin system fuels intracardiac parasitism and worsens heart pathology in experimental chagas disease","volume":"8","author":"Nascimento","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000358734","article-title":"Basophils: Historical reflections and perspectives","volume":"100","author":"Marone","year":"2014","journal-title":"Chem. Immunol. Allergy."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1074\/mcp.M114.046946","article-title":"A human platelet receptor protein microarray identifies the high affinity immunoglobulin E receptor subunit alpha (FcepsilonR1alpha) as an activating platelet endothelium aggregation receptor 1 (PEAR1) ligand","volume":"14","author":"Sun","year":"2015","journal-title":"Mol. Cell Proteom."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"478","DOI":"10.4049\/jimmunol.135.1.478","article-title":"Anti-IgE autoantibody in patients with atopic dermatitis","volume":"135","author":"Nawata","year":"1985","journal-title":"J. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0190-9622(99)70495-0","article-title":"Chronic idiopathic urticaria: comparison of the clinical features of patients with and without anti-FcepsilonRI or anti-IgE autoantibodies","volume":"40","author":"Sabroe","year":"1999","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/1523-1747.ep12462239","article-title":"Prevalence and functional role of anti-IgE autoantibodies in urticarial syndromes","volume":"90","author":"Gruber","year":"1988","journal-title":"J. Investig. Dermatol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1016\/j.jaci.2016.04.007","article-title":"Role of IgE in autoimmunity","volume":"137","author":"Sanjuan","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_105","first-page":"11","article-title":"Angiogenesis, lymphangiogenesis and clinical implications. Preface","volume":"99","author":"Marone","year":"2014","journal-title":"Chem. Immunol. Allergy."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1161\/CIRCULATIONAHA.110.957332","article-title":"Vascular endothelial growth factor-B acts as a coronary growth factor in transgenic rats without inducing angiogenesis, vascular leak, or inflammation","volume":"122","author":"Bry","year":"2010","journal-title":"Circulation"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.coi.2018.05.011","article-title":"Dendritic cells in inflammatory angiogenesis and lymphangiogenesis","volume":"53","author":"Bosisio","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s10238-018-0493-6","article-title":"Mast cells and angiogenesis in pancreatic ductal adenocarcinoma","volume":"18","author":"Longo","year":"2018","journal-title":"Clin. Exp. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3389\/fimmu.2018.00527","article-title":"Contribution to tumor angiogenesis from innate immune cells within the tumor microenvironment: Implications for immunotherapy","volume":"9","author":"Albini","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"eaan4626","DOI":"10.1126\/sciimmunol.aan4626","article-title":"Neuropilin-1 expression in adipose tissue macrophages protects against obesity and metabolic syndrome","volume":"3","author":"Wilson","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.mehy.2011.01.012","article-title":"The grossly invisible and generally ignored lymphatics of the mammalian heart","volume":"76","author":"Miller","year":"2011","journal-title":"Med. Hypotheses"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1161\/CIRCRESAHA.115.306544","article-title":"Lymphatic system in cardiovascular medicine","volume":"118","author":"Aspelund","year":"2016","journal-title":"Circ. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1365-2362.2010.02431.x","article-title":"Lymphatic vasculature is increased in heart valves, ischaemic and inflamed hearts and in cholesterol-rich and calcified atherosclerotic lesions","volume":"41","author":"Kholova","year":"2011","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/ca.22638","article-title":"Anatomy and development of the cardiac lymphatic vasculature: Its role in injury and disease","volume":"29","author":"Norman","year":"2016","journal-title":"Clin. Anat."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nm.1960","article-title":"Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism","volume":"15","author":"Machnik","year":"2009","journal-title":"Nat. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1172\/JCI60113","article-title":"Immune cells control skin lymphatic electrolyte homeostasis and blood pressure","volume":"123","author":"Wiig","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4899","DOI":"10.1172\/JCI77483","article-title":"VEGF-C and aortic cardiomyocytes guide coronary artery stem development","volume":"124","author":"Chen","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1056\/NEJMra010082","article-title":"Infective endocarditis in adults","volume":"345","author":"Mylonakis","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"6","DOI":"10.21037\/atm.2017.12.26","article-title":"Severe sepsis and cardiac arrhythmias","volume":"6","author":"Shahreyar","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.3389\/fimmu.2018.02011","article-title":"Essential domain-dependent roles within soluble IgG for in vivo superantigen properties of staphylococcal Protein A: Resolving the B-Cell Superantigen paradox","volume":"9","author":"Goodyear","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/BF02912454","article-title":"Metabolic and hemodynamic effects of peptide leukotriene C4 and D4 in man","volume":"27","author":"Vigorito","year":"1997","journal-title":"Int. J. Clin. Lab. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1161\/01.RES.49.2.545","article-title":"The arrhythmogenic actions of histamine on human atrial fibers","volume":"49","author":"Levi","year":"1981","journal-title":"Circ. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1161\/01.CIR.73.6.1175","article-title":"Effect of activation of the H1 receptor on coronary hemodynamics in man","volume":"73","author":"Vigorito","year":"1986","journal-title":"Circulation"},{"key":"ref_124","first-page":"719","article-title":"Effect of PGD2 on cardiac contractility: A negative inotropism secondary to coronary vasoconstriction conceals a primary positive inotropic action","volume":"237","author":"Hattori","year":"1986","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0042-6822(87)90449-1","article-title":"Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins","volume":"156","author":"Gelderblom","year":"1987","journal-title":"Virology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/j.jacc.2012.02.024","article-title":"Sudden cardiac death in patients with human immunodeficiency virus infection","volume":"59","author":"Tseng","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"302638","DOI":"10.1155\/2015\/302638","article-title":"Cardiovascular complications of HIV-associated immune dysfunction","volume":"2015","author":"Zaaqoq","year":"2015","journal-title":"Cardiol. Res. Pract."},{"key":"ref_128","first-page":"1345","article-title":"Stress, inflammation and natural treatments","volume":"32","author":"Theoharides","year":"2018","journal-title":"J. Biol. Regul. Homeost Agents"},{"key":"ref_129","first-page":"763","article-title":"Impact of mold on mast cell-cytokine immune response","volume":"32","author":"Kritas","year":"2018","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e00246-17","DOI":"10.1128\/IAI.00246-17","article-title":"Differential regulation of mas-related G Protein-coupled receptor X2-mediated mast cell degranulation by antimicrobial host defense peptides and porphyromonas gingivalis Lipopolysaccharide","volume":"85","author":"Gupta","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_131","first-page":"787","article-title":"IgE myeloma. Report of a new case and review of the literature","volume":"66","author":"Sala","year":"1981","journal-title":"Haematologica"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1128\/iai.55.3.803-809.1987","article-title":"Mechanism of activation of human basophils by Staphylococcus aureus Cowan 1","volume":"55","author":"Marone","year":"1987","journal-title":"Infect. Immun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.4049\/jimmunol.161.10.5647","article-title":"Endogenous superallergen protein Fv induces IL-4 secretion from human Fc epsilon RI+ cells through interaction with the VH3 region of IgE","volume":"161","author":"Patella","year":"1998","journal-title":"J. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0003-2697(74)90093-1","article-title":"An automated continuous-flow system for the extraction and fluorometric analysis of histamine","volume":"57","author":"Siraganian","year":"1974","journal-title":"Anal. Biochem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"4278","DOI":"10.4049\/jimmunol.147.12.4278","article-title":"Characterization of the anti-inflammatory effect of FK-506 on human mast cells","volume":"147","author":"Cirillo","year":"1991","journal-title":"J. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.3389\/fimmu.2018.01721","article-title":"Secreted phospholipases A2 in hereditary angioedema with C1-inhibitor deficiency","volume":"9","author":"Loffredo","year":"2018","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/8\/1828\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:45:04Z","timestamp":1760186704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/8\/1828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,12]]},"references-count":136,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["ijms20081828"],"URL":"https:\/\/doi.org\/10.3390\/ijms20081828","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,12]]}}}