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The release of web-like DNA structures named neutrophil extracellular traps (NETs) constitutes an important mechanism by which neutrophils prevent pathogen dissemination or deal with microorganisms of a bigger size. At the same time, nuclear and granule proteins with microbicidal activity bind to these DNA structures promoting the elimination of entrapped pathogens. However, these toxic properties may produce unwanted effects in the host, when neutrophils uncontrollably release NETs upon persistent inflammation. As a consequence, NET accumulation can produce vessel occlusion, tissue damage, and prolonged inflammation associated with the progression and exacerbation of multiple pathologic conditions. This review outlines recent advances in understanding the mechanisms of NET release and functions in sterile disease. We also discuss mechanisms of physiological regulation and the importance of neutrophil heterogeneity in NET formation and composition.<\/jats:p>","DOI":"10.1093\/cvr\/cvab329","type":"journal-article","created":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T18:52:38Z","timestamp":1634064758000},"page":"2737-2753","source":"Crossref","is-referenced-by-count":403,"title":["Neutrophil extracellular traps: from physiology to pathology"],"prefix":"10.1093","volume":"118","author":[{"given":"Andres","family":"Hidalgo","sequence":"first","affiliation":[{"name":"Area of Cell and Developmental Biology, Fundaci\u00f3n Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) , Melchor Fern\u00e1ndez Almagro 3, 28029, Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-502X","authenticated-orcid":false,"given":"Peter","family":"Libby","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , 75 Francis Street, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Soehnlein","sequence":"additional","affiliation":[{"name":"Institute for Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), University of M\u00fcnster , Von-Esmarch-Stra\u00dfe 56, 48149, M\u00fcnster ,","place":["Germany"]},{"name":"Department of Physiology and Pharmacology (FyFa), Karolinska Institute , Solnav\u00e4gen 1, 171 77, Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2363-4770","authenticated-orcid":false,"given":"Iker Valle","family":"Aramburu","sequence":"additional","affiliation":[{"name":"Laboratory of Antimicrobial Defence, The Francis Crick Institute , London NW1 1AT 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