{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:08:52Z","timestamp":1792804132643,"version":"4.5.0"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHA 2040\/1-1; SCHE1583714-1; TRR241: project B04; CRC1181: projects C03, A01, Z02; FOR 2886 projects A03, B03"],"award-info":[{"award-number":["SCHA 2040\/1-1; SCHE1583714-1; TRR241: project B04; CRC1181: projects C03, A01, Z02; FOR 2886 projects A03, B03"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["H2020-MSCE-RISE-2015 project Nr. 690836 PANG; ERC-Synergy grant 4D Nanoscope"],"award-info":[{"award-number":["H2020-MSCE-RISE-2015 project Nr. 690836 PANG; ERC-Synergy grant 4D Nanoscope"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001663","name":"Volkswagen Foundation","doi-asserted-by":"publisher","award":["Grant 97744"],"award-info":[{"award-number":["Grant 97744"]}],"id":[{"id":"10.13039\/501100001663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF)","award":["C.S."],"award-info":[{"award-number":["C.S."]}]},{"name":"ELAN of Friedrich-Alexander-University of Erlangen-N\u00fcrnberg","award":["C.S."],"award-info":[{"award-number":["C.S."]}]},{"name":"Optical Imaging Center Erlangen (OICE)","award":["C.S."],"award-info":[{"award-number":["C.S."]}],"id":[{"id":"https:\/\/ror.org\/05hsqsk33","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Margarete Ammon Foundation Munich","award":["C.S."],"award-info":[{"award-number":["C.S."]}]},{"name":"Manfred Roth-Foundation F\u00fcrth","award":["C.S."],"award-info":[{"award-number":["C.S."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Salivary gland stones, or sialoliths, are the most common cause of the obstruction of salivary glands. The mechanism behind the formation of sialoliths has been elusive. Symptomatic sialolithiasis has a prevalence of 0.45% in the general population, is characterized by recurrent painful periprandial swelling of the affected gland, and often results in sialadenitis with the need for surgical intervention. Here, we show by the use of immunohistochemistry, immunofluorescence, computed tomography (CT) scans and reconstructions, special dye techniques, bacterial genotyping, and enzyme activity analyses that neutrophil extracellular traps (NETs) initiate the formation and growth of sialoliths in humans. The deposition of neutrophil granulocyte extracellular DNA around small crystals results in the dense aggregation of the latter, and the subsequent mineralization creates alternating layers of dense mineral, which are predominantly calcium salt deposits and DNA. The further agglomeration and appositional growth of these structures promotes the development of macroscopic sialoliths that finally occlude the efferent ducts of the salivary glands, causing clinical symptoms and salivary gland dysfunction. These findings provide an entirely novel insight into the mechanism of sialolithogenesis, in which an immune system-mediated response essentially participates in the physicochemical process of concrement formation and growth.<\/jats:p>","DOI":"10.3390\/cells9092139","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T02:56:43Z","timestamp":1600916203000},"page":"2139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Neutrophil Extracellular Traps Promote the Development and Growth of Human Salivary Stones"],"prefix":"10.3390","volume":"9","author":[{"given":"Mirco","family":"Schapher","sequence":"first","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Otolaryngology, Head and Neck Surgery, Universit\u00e4tsklinikum Erlangen, Waldstrasse 1, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Koch","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Otolaryngology, Head and Neck Surgery, Universit\u00e4tsklinikum Erlangen, Waldstrasse 1, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Weidner","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-6785","authenticated-orcid":false,"given":"Michael","family":"Scholz","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Institute of Functional and Clinical Anatomy, Universit\u00e4tsstrasse 19, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wirtz","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 1, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irmgard","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeeshan","family":"Singh","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 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":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Leppkes","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 1, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Schauer","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Gr\u00fcneboom","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Alexiou","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Otolaryngology, Head and Neck Surgery, Universit\u00e4tsklinikum Erlangen, Waldstrasse 1, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Iro","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Otolaryngology, Head and Neck Surgery, Universit\u00e4tsklinikum Erlangen, Waldstrasse 1, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5395-804X","authenticated-orcid":false,"given":"Luis E.","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0258-2484","authenticated-orcid":false,"given":"Martin","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Deutsches Zentrum f\u00fcr Immuntherapie, Universit\u00e4tsklinikum Erlangen, Ulmenweg 18, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"ref_1","first-page":"349","article-title":"C\u00e0lculos salivales salivary calculi anales espa\u00f1oles de odontoestomatologia","volume":"2","year":"1948","journal-title":"Illus 15 Excerpta Med."},{"key":"ref_2","first-page":"661","article-title":"Calculos salivales [Salivary calculi]","volume":"7","year":"1948","journal-title":"Esp. Odontoestomatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"McGurk, M.C.L. (2013). Controversies in the Management of Salivary Gland Disease, Oxford University Press. [2nd ed.].","DOI":"10.1093\/med\/9780199578207.001.0001"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/sj.bdj.2014.1054","article-title":"Salivary stones: Symptoms, aetiology, biochemical composition and treatment","volume":"217","author":"Kraaij","year":"2014","journal-title":"Br. Dent. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1002\/lary.25377","article-title":"Nearly 3000 salivary stones: Some clinical and epidemiologic aspects","volume":"125","author":"Sigismund","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0003-9969(89)90066-6","article-title":"The presence of microcalculi in normal human submandibular and parotid salivary glands","volume":"34","author":"Epivatianos","year":"1989","journal-title":"Arch. Oral Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1600-0714.1978.tb01882.x","article-title":"The prevalence of consolidated salivary deposits in the small ducts of human submandibular glands","volume":"7","author":"Scott","year":"1978","journal-title":"J. Oral Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.tripleo.2004.12.023","article-title":"Lithiasis of minor salivary glands: Current data","volume":"100","author":"Alantar","year":"2005","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0901-5027(05)80127-4","article-title":"Sialolithiasis. A survey on 245 patients and a review of the literature","volume":"19","author":"Lustmann","year":"1990","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1001\/archoto.2010.238","article-title":"Sialoendoscopy: Prognostic factors for endoscopic removal of salivary stones","volume":"137","author":"Luers","year":"2011","journal-title":"Arch Otolaryngol. Head Neck Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1016\/j.ultrasmedbio.2019.05.019","article-title":"Transoral Ultrasound in the Diagnosis of Obstructive Salivary Gland Pathologies","volume":"45","author":"Schapher","year":"2019","journal-title":"Ultrasound Med Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1177\/0194599812452837","article-title":"Sialendoscopy in the diagnosis and treatment of sialolithiasis: A study on more than 1000 patients","volume":"147","author":"Zenk","year":"2012","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00106-009-2075-0","article-title":"Modern concepts for the diagnosis and therapy of sialolithiasis","volume":"58","author":"Iro","year":"2010","journal-title":"HNO"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1177\/0194599818775946","article-title":"Ultrasound Supplemented by Sialendoscopy: Diagnostic Value in Sialolithiasis","volume":"159","author":"Goncalves","year":"2018","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Koch, M., Schapher, M., Mantsopoulos, K., Goncalves, M., and Iro, H. (2018). Intraductal Pneumatic Lithotripsy after Extended Transoral Duct Surgery in Submandibular Sialolithiasis. Otolaryngol. Head Neck Surg.","DOI":"10.1177\/0194599818802224"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/lary.27037","article-title":"Multimodal treatment in difficult sialolithiasis: Role of extracorporeal shock-wave lithotripsy and intraductal pneumatic lithotripsy","volume":"128","author":"Koch","year":"2018","journal-title":"Laryngoscope"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1002\/lary.26459","article-title":"Transoral submandibulotomy for deep hilar submandibular gland sialolithiasis","volume":"127","author":"Schapher","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1007\/s00405-012-2286-y","article-title":"Combined endoscopic-transcutaneous surgery in parotid gland sialolithiasis and other ductal diseases: Reporting medium- to long-term objective and patients\u2019 subjective outcomes","volume":"270","author":"Koch","year":"2013","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_19","first-page":"5548","article-title":"Intraductal lithotripsy in sialolithiasis with two different Ho:YAG lasers: Presetting parameters, effectiveness, success rates","volume":"23","author":"Koch","year":"2019","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.otc.2009.08.002","article-title":"Algorithms for treatment of salivary gland obstructions","volume":"42","author":"Koch","year":"2009","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1017\/S002221511600966X","article-title":"Does saliva composition affect the formation of sialolithiasis?","volume":"131","author":"Schroder","year":"2017","journal-title":"J. Laryngol. Otol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1001\/archotol.127.1.66","article-title":"Retrograde theory in sialolithiasis formation","volume":"127","author":"Marchal","year":"2001","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.otc.2009.08.012","article-title":"Causes, natural history, and incidence of salivary stones and obstructions","volume":"42","author":"Harrison","year":"2009","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/BF01606428","article-title":"Histochemical and biochemical determination of calcium in salivary glands with particular reference to chronic submandibular sialadenitis","volume":"423","author":"Harrison","year":"1993","journal-title":"Virchows Arch. A Pathol. Anat. Histopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s001060050476","article-title":"Clinical and diagnostic findings of sialolithiasis","volume":"47","author":"Zenk","year":"1999","journal-title":"HNO"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.coms.2009.04.005","article-title":"Diagnostic imaging in sialadenitis","volume":"21","author":"Zenk","year":"2009","journal-title":"Oral Maxillofac. Surg. Clin. N. Am."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/0003-9969(81)90173-4","article-title":"Lipids associated with mineralization of human submandibular gland sialoliths","volume":"26","author":"Boskey","year":"1981","journal-title":"Arch. Oral Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/0003-9969(82)90191-1","article-title":"Lipid composition of the matrix of human submandibular salivary gland stones","volume":"27","author":"Slomiany","year":"1982","journal-title":"Arch. Oral Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/0003-9969(83)90015-8","article-title":"Phospholipids associated with human parotid gland sialoliths","volume":"28","author":"Boskey","year":"1983","journal-title":"Arch. Oral Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1600-0714.1993.tb01089.x","article-title":"Ultrastructural localization of microliths in salivary glands of cat","volume":"22","author":"Harrison","year":"1993","journal-title":"J. Oral Pathol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.archoralbio.2005.01.008","article-title":"Organic secretory products, adaptive responses and innervation in the parotid gland of ferret: A histochemical study","volume":"50","author":"Triantafyllou","year":"2005","journal-title":"Arch. Oral Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0030-4220(92)90104-X","article-title":"Production of microliths and sialadenitis in rats by a short combined course of isoprenaline and calcium gluconate","volume":"73","author":"Harrison","year":"1992","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.joms.2003.08.041","article-title":"Chronic recurrent parotitis: A closer look at its origin, diagnosis, and management","volume":"62","author":"Baurmash","year":"2004","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1097\/01.mlg.0000157832.23380.df","article-title":"Sialoendoscopic and irrigation findings in chronic obstructive parotitis","volume":"115","author":"Qi","year":"2005","journal-title":"Laryngoscope"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"De Grandi, R., Capaccio, P., Bidossi, A., Bottagisio, M., Drago, L., Torretta, S., Pignataro, L., and De Vecchi, E. (2018). Salivary calculi microbiota: New insights into microbial networks and pathogens reservoir. Microbes. Infect.","DOI":"10.1016\/j.micinf.2018.10.002"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1259\/dmfr\/24118767","article-title":"Salivary duct strictures: Nature and incidence in benign salivary obstruction","volume":"36","author":"Ngu","year":"2007","journal-title":"Dentomaxillofac. Radiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bjoms.2014.09.017","article-title":"Incidence of different causes of benign obstruction of the salivary glands: Retrospective analysis of 493 cases using fluoroscopy and digital subtraction sialography","volume":"53","author":"Lee","year":"2015","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1023\/A:1018870511257","article-title":"Activation of human neutrophils by calcium carbonate polymorphs","volume":"42","author":"Burt","year":"1997","journal-title":"Dig. Dis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/ncomms10274","article-title":"Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis","volume":"7","author":"Mulay","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.immuni.2019.07.002","article-title":"Neutrophil Extracellular Traps Initiate Gallstone Formation","volume":"51","author":"Munoz","year":"2019","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"376","DOI":"10.3389\/fimmu.2012.00376","article-title":"Bonding the foe\u2014NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals","volume":"3","author":"Schorn","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"583","DOI":"10.3389\/fimmu.2016.00583","article-title":"Menage-a-Trois: The Ratio of Bicarbonate to CO2 and the pH Regulate the Capacity of Neutrophils to Form NETs","volume":"7","author":"Maueroder","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Munoz, L.E., Bilyy, R., Biermann, M.H.C., Kienhofer, D., Maueroder, C., Hahn, J., Brauner, J.M., Weidner, D., Chen, J., and Scharin-Mehlmann, M. (2016). Nanoparticles size-dependently initiate self-limiting NETosis-driven inflammation. Proc. Natl. Acad. Sci. USA, 113.","DOI":"10.1073\/pnas.1602230113"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rada, B. (2017). Neutrophil Extracellular Traps and Microcrystals. J. Immunol. Res.","DOI":"10.1155\/2017\/2896380"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fimmu.2016.00302","article-title":"New insights into Neutrophil extracellular Traps: Mechanisms of Formation and Role in inflammation","volume":"7","author":"Yang","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00109-015-1295-x","article-title":"How neutrophil extracellular traps orchestrate the local immune response in gout","volume":"93","author":"Maueroder","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nm.3547","article-title":"Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines","volume":"20","author":"Schauer","year":"2014","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1038\/nm.4217","article-title":"Reply to \u201cNeutrophils are not required for resolution of acute gouty arthritis in mice\u201d","volume":"22","author":"Reinwald","year":"2016","journal-title":"Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10973","DOI":"10.1038\/ncomms10973","article-title":"Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis","volume":"7","author":"Leppkes","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1002\/JLB.HI0718-249RR","article-title":"Frontline Science: Aggregated neutrophil extracellular traps prevent inflammation on the neutrophil-rich ocular surface","volume":"105","author":"Mahajan","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.media.2016.06.016","article-title":"Shaping the future through innovations: From medical imaging to precision medicine","volume":"33","author":"Comaniciu","year":"2016","journal-title":"Med. Image Anal."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ali, M.J., Scholz, M., Singh, S., Heichel, J., and Paulsen, F. (2020). Etiopathogenesis of lacrimal sac mucopeptide concretions: Insights from cinematic rendering techniques. Graefes Arch. Clin. Exp. Ophthalmol.","DOI":"10.1007\/s00417-020-04793-7"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1681\/ASN.2016020232","article-title":"Fully Automated Evaluation of Total Glomerular Number and Capillary Tuft Size in Nephritic Kidneys Using Lightsheet Microscopy","volume":"28","author":"Klingberg","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pickert, G., Wirtz, S., Matzner, J., Ashfaq-Khan, M., Heck, R., Rosigkeit, S., Thies, D., Surabattula, R., Ehmann, D., and Wehkamp, J. (2020). Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor-mediated Dysbiosis. Gastroenterology.","DOI":"10.1053\/j.gastro.2020.03.064"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nmeth.2604","article-title":"UPARSE: Highly accurate OTU sequences from microbial amplicon reads","volume":"10","author":"Edgar","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1017\/S1431927613001694","article-title":"Structure and growth of sialoliths: Computed microtomography and electron microscopy investigation of 30 specimens","volume":"19","author":"Nolasco","year":"2013","journal-title":"Microsc. Microanal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1017\/S1431927618016124","article-title":"Mineralization of Sialoliths Investigated by Ex Vivo and In Vivo X-ray Computed Tomography","volume":"25","author":"Nolasco","year":"2019","journal-title":"Microsc. Microanal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nm.4294","article-title":"An emerging role for neutrophil extracellular traps in noninfectious disease","volume":"23","author":"Jorch","year":"2017","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15003","DOI":"10.1038\/s41598-017-15106-0","article-title":"Particles of different sizes and shapes induce neutrophil necroptosis followed by the release of neutrophil extracellular trap-like chromatin","volume":"7","author":"Desai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/cre2.158","article-title":"Presence of Streptococcus dentisani in the dental plaque of children from different Colombian cities","volume":"5","author":"Diaz","year":"2019","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1128\/jcm.30.1.243-244.1992","article-title":"Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus (the Streptococcus milleri group): Association with different body sites and clinical infections","volume":"30","author":"Whiley","year":"1992","journal-title":"J. Clin. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Lukic, D., Karygianni, L., Flury, M., Attin, T., and Thurnheer, T. (2020). Endodontic-Like Oral Biofilms as Models for Multispecies Interactions in Endodontic Diseases. Microorganisms, 8.","DOI":"10.3390\/microorganisms8050674"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kriem, L.S., Wright, K., Ccahuana-Vasquez, R.A., and Rupp, S. (2020). Confocal Raman microscopy to identify bacteria in oral subgingival biofilm models. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232912"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1099\/ijs.0.2008\/000810-0","article-title":"Dialister succinatiphilus sp. nov. and Barnesiella intestinihominis sp. nov., isolated from human faeces","volume":"58","author":"Morotomi","year":"2008","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3389\/fmicb.2020.00439","article-title":"Evolution of the Gut Microbiome in Early Childhood: A Cross-Sectional Study of Chinese Children","volume":"11","author":"Niu","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1097\/MAO.0000000000002355","article-title":"Microbiome Analysis of Cholesteatoma by Gene Sequencing","volume":"40","author":"Weiss","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF00163813","article-title":"Analytical ultrastructural investigation of microliths in salivary glands of cat","volume":"25","author":"Triantafyllou","year":"1993","journal-title":"Histochem. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/lary.27860","article-title":"Evidence of a microbial etiology for sialoliths","volume":"130","author":"Kao","year":"2020","journal-title":"Laryngoscope"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Harrison, J.D. (2019). Regarding the Lack of Evidence for a Microbial Etiology of Sialolithiasis. Laryngoscope, 129.","DOI":"10.1002\/lary.28047"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0003-9969(02)00211-X","article-title":"Sialolith crystals localized intraglandularly and in the Wharton\u2019s duct of the human submandibular gland: An X-ray diffraction analysis","volume":"48","author":"Teymoortash","year":"2003","journal-title":"Arch. Oral Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature12942","article-title":"Citrullination regulates pluripotency and histone H1 binding to chromatin","volume":"507","author":"Christophorou","year":"2014","journal-title":"Nature"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/9\/2139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:12:16Z","timestamp":1760177536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/9\/2139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,22]]},"references-count":71,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["cells9092139"],"URL":"https:\/\/doi.org\/10.3390\/cells9092139","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,22]]}}}