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Mechanisms of regulation, however, are incompletely understood. The aim of the study was to elucidate the role of interferon gamma (IFN-\u03b3) in the orchestrated inflammatory response in a murine model of MI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>MI was induced in 8- to 12-week-old male mice (C57BL\/6 background) by permanent ligation of the left anterior descending (LAD) coronary artery. Lysozyme M (LysM)+ cell-depleted LysMiDTR transgenic mice displayed a reduced influx of CD45.2+\/CD3\u2212\/CD11b+\/Gr-1high neutrophils into infarcted myocardium 1 day post-MI compared with infarcted controls, paralleled by decreased cardiac mRNA levels of IFN-\u03b3 and tumour necrosis factor alpha (TNF-\u03b1). Mortality after MI was significantly increased in LysM+ cell-depleted mice within 28 days post-MI. To more specifically address the role of neutrophils, we depleted C57BL\/6 mice with a monoclonal anti-Gr-1 antibody and found increased mortality, deteriorated cardiac function as well as decreased cardiac IFN-\u03b3 mRNA expression early after MI. Ccl2, Cxcl1, Cx3cl1, and Il12b mRNA were reduced 3 days after MI, as was the amount of CD11b+\/Ly-6G\u2212\/Ly-6Chigh inflammatory monocytes. LAD-ligated Cramp\u2212\/\u2212 mice lacking cathelicidin important in neutrophil-dependent monocyte chemotaxis as well as IFN\u03b3\u2212\/\u2212 and TNF\u03b1\u2212\/\u2212 mice phenocopied Gr-1+ cell-depleted mice, supporting a regulatory role of IFN-\u03b3 impacting on both the sequence of inflammatory cell invasion and cardiac outcome early after MI. The use of conditional IFN-\u03b3 receptor deficient mice indicated a direct effect of IFN-\u03b3 on LysM+ cells in cardiac injury post-MI. Using IFN-\u03b3 reporter mice and flow cytometry, we identified cardiac lymphoid cells (CD4+ and CD8+ T cells and natural killer cells) as primary source of this cytokine in the cardiac inflammatory response post-MI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>IFN-\u03b3 directs a sequential chemotactic cellular immune response and determines survival and cardiac function post-MI.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvz092","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T15:24:41Z","timestamp":1554218681000},"page":"1907-1917","source":"Crossref","is-referenced-by-count":43,"title":["A sequential interferon gamma directed chemotactic cellular immune response determines survival and cardiac function post-myocardial infarction"],"prefix":"10.1093","volume":"115","author":[{"given":"Stefanie","family":"Finger","sequence":"first","affiliation":[{"name":"Center for Cardiology\u2014Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner site RheinMain, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Knorr","sequence":"additional","affiliation":[{"name":"Center for Cardiology\u2014Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Molitor","sequence":"additional","affiliation":[{"name":"Center for Cardiology\u2014Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner site RheinMain, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sch\u00fcler","sequence":"additional","affiliation":[{"name":"Center for Cardiology\u2014Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"Institute for Molecular Medicine, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata","family":"Garlapati","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner site RheinMain, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Waisman","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Brandt","sequence":"additional","affiliation":[{"name":"Center for Cardiology\u2014Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"M\u00fcnzel","sequence":"additional","affiliation":[{"name":"Center for Cardiology\u2014Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner site RheinMain, University Medical Center Mainz, Langenbeckstra\u00dfe 1, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bopp","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Mainz, Langenbeckstra\u00dfe, 1, Mainz, 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