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The mechanism behind dacryolithiasis remains unclear; however, the involvement of various immune cells, including neutrophils, has been confirmed. These findings remain limited, and no information on neutrophil extracellular traps (NETs), essentially involved in the pathogenesis of other lithiases, is available yet. Here, we employ microcomputed tomography, magnetic resonance tomography, histochemistry, mass spectrometry, and enzyme activity analyses to investigate the role of neutrophils and NETs in dacryolithiasis. We classify mucopeptide concretions into three types, with respect to the quantity of cellular and acellular material, polysaccharides, and mucosubstances. We propose the role of neutrophils and NETs within the existing model of gradual formation and growth of mucopeptide concretions, with neutrophils contributing to the initial stages of dacryolithiasis, as they localized on the inner (older) parts of the tissue. As NETs localized on the outer (newer) parts of the tissue, we link their role to the late stages of dacryolithiasis, presumably maintaining the proinflammatory environment and preventing efficient clearance. An abundance of IgG on the surface indicates the involvement of the adaptive immune system later as well. These findings bring new perspectives on dacryolithiasis, in which the innate and adaptive immune system are essentially involved.<\/jats:p>","DOI":"10.3390\/cells12141857","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T08:35:47Z","timestamp":1689323747000},"page":"1857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neutrophil Extracellular Traps Drive Dacryolithiasis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-8259","authenticated-orcid":false,"given":"Leticija","family":"Zlatar","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-7537","authenticated-orcid":false,"given":"Thomas","family":"Timm","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0377-395X","authenticated-orcid":false,"given":"G\u00fcnter","family":"Lochnit","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-1349","authenticated-orcid":false,"given":"Rostyslav","family":"Bilyy","sequence":"additional","affiliation":[{"name":"Department of Histology, Cytology, Embryology, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-6199","authenticated-orcid":false,"given":"Tobias","family":"B\u00e4uerle","sequence":"additional","affiliation":[{"name":"Institute of Radiology, Preclinical Imaging Platform Erlangen (PIPE), Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Munoz-Becerra","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-9370","authenticated-orcid":false,"given":"Jasmin","family":"Knopf","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Universit\u00e4tsklinikum Erlangen, Friedrich Alexander University Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Department of Pediatric Surgery, University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Heichel","sequence":"additional","affiliation":[{"name":"Department and Policlinic of Ophthalmology, Martin Luther University of Halle-Wittenberg, 06108 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Javed","family":"Ali","sequence":"additional","affiliation":[{"name":"Govindram Seksaria Institute of Dacryology, L.V. 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