{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T17:06:54Z","timestamp":1748020014202,"version":"3.37.3"},"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019023","name":"Gesellschaft zur F\u00f6rderung Kynologischer Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019023","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in <jats:italic>ex vivo<\/jats:italic> samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3\/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (<jats:italic>p<\/jats:italic> &lt; 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies.<\/jats:p>","DOI":"10.1371\/journal.pone.0295268","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T18:35:13Z","timestamp":1705689313000},"page":"e0295268","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neutrophil extracellular traps in CSF and serum of dogs with steroid-responsive meningitis-arteritis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2009-6682","authenticated-orcid":true,"given":"Jan Christian","family":"Wohlsein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marita","family":"Meurer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"M\u00f6rgelin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmin Nicole","family":"Nessler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Flegel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning Christian","family":"Schenk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad","family":"Jurina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Rentmeister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"G\u00f6dde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Baumg\u00e4rtner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maren","family":"von K\u00f6ckritz-Blickwede","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Tipold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"issue":"3","key":"pone.0295268.ref001","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1748-5827.2009.00848.x","article-title":"An update on steroid responsive meningitis-arteritis","volume":"51","author":"A Tipold","year":"2010","journal-title":"J Small Anim Pract"},{"issue":"5","key":"pone.0295268.ref002","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cvsm.2010.05.008","article-title":"Inflammatory Diseases of the Spine in Small Animals","volume":"40","author":"A Tipold","year":"2010","journal-title":"Vet Clin North Am Small Anim Pract"},{"issue":"1","key":"pone.0295268.ref003","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1939-1676.1988.tb01974.x","article-title":"Canine meningitis. A changing emphasis","volume":"2","author":"SM Meric","year":"1988","journal-title":"J Vet Intern Med"},{"issue":"2","key":"pone.0295268.ref004","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/jsap.12938","article-title":"Pyrexia in juvenile dogs: a review of 140 referred cases","volume":"60","author":"VL Black","year":"2019","journal-title":"J Small Anim Pract"},{"issue":"11","key":"pone.0295268.ref005","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1136\/vr.105818","article-title":"Clinical reasoning in canine cervical hyperaesthesia: which presenting features are important?","volume":"187","author":"NJ Grapes","year":"2020","journal-title":"Vet Rec"},{"issue":"7","key":"pone.0295268.ref006","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/j.1748-5827.2006.00042.x","article-title":"Retrospective study of fever in dogs: laboratory testing, diagnoses and influence of prior treatment","volume":"47","author":"IA Battersby","year":"2006","journal-title":"J Small Anim Pract"},{"issue":"11","key":"pone.0295268.ref007","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/jsap.12143","article-title":"Screening diagnostics to identify triggers in 21 cases of steroid-responsive meningitis-arteritis","volume":"54","author":"JH Rose","year":"2013","journal-title":"J Small Anim Pract"},{"issue":"7","key":"pone.0295268.ref008","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1748-5827.2000.tb03205.x","article-title":"Long-term treatment of dogs with steroid-responsive meningitis-arteritis: clinical, laboratory and therapeutic results","volume":"41","author":"S Cizinauskas","year":"2000","journal-title":"J Small Anim Pract"},{"issue":"6","key":"pone.0295268.ref009","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1748-5827.1994.tb03293.x","article-title":"Steroid responsive meningitis-arteritis in dogs: Long-term study of 32 cases","volume":"35","author":"A Tipold","year":"1994","journal-title":"J Small Anim Pract"},{"issue":"4","key":"pone.0295268.ref010","first-page":"350","article-title":"A retrospective epidemiological study of clinical signs and familial predisposition associated with aseptic meningitis in the Norwegian population of Nova Scotia duck tolling retrievers born 1994\u20132003","volume":"72","author":"KP Anfinsen","year":"2008","journal-title":"Can J Vet Res"},{"key":"pone.0295268.ref011","first-page":"185","article-title":"Steril-eitrige Meningitis-Arteriitis (SRMA) bei drei Wurfgeschwistern der Rasse Petit Basset Griffon Vend\u00e9en","volume":"57","author":"J Voss","year":"2012","journal-title":"Kleintierpraxis"},{"key":"pone.0295268.ref012","first-page":"281","volume-title":"Veterinary Neuranatomy and Clinical Neurology","author":"A DeLahunta","year":"2009","edition":"3"},{"issue":"4","key":"pone.0295268.ref013","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1111\/j.1939-1676.2009.0337.x","article-title":"Steroid Responsive Meningitis-Arteritis: A Prospective Study of Potential Disease Markers, Prednisolone Treatment, and Long-Term Outcome in 20 Dogs (2006\u20132008)","volume":"23","author":"M Lowrie","year":"2009","journal-title":"J Vet Intern Med"},{"issue":"5","key":"pone.0295268.ref014","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1111\/j.1939-1676.2008.0164.x","article-title":"Concentrations of Acute-Phase Proteins in Dogs with Steroid Responsive Meningitis-Arteritis","volume":"22","author":"A Bathen-Noethen","year":"2008","journal-title":"J Vet Intern Med"},{"key":"pone.0295268.ref015","doi-asserted-by":"crossref","first-page":"105692","DOI":"10.1016\/j.tvjl.2021.105692","article-title":"Biomarkers of non-infectious inflammatory CNS diseases in dogs: Where are we now? Part 2\u2014Steroid responsive meningitis-arteritis","volume":"273","author":"E Andersen-Ranberg","year":"2021","journal-title":"Vet J"},{"issue":"3\u20134","key":"pone.0295268.ref016","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.vetimm.2008.07.007","article-title":"Selective CD11a upregulation on neutrophils in the acute phase of steroid-responsive meningitis-arteritis in dogs","volume":"126","author":"M Schwartz","year":"2008","journal-title":"Vet Immunol Immunopathol"},{"issue":"2","key":"pone.0295268.ref017","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.tvjl.2010.12.018","article-title":"Determination of immunoglobulin A concentrations in the serum and cerebrospinal fluid of dogs: an estimation of its diagnostic value in canine steroid-responsive meningitis-arteritis","volume":"191","author":"A Maiolini","year":"2012","journal-title":"Vet J"},{"key":"pone.0295268.ref018","first-page":"73","volume-title":"Veterinary Neuropathology: Essentials of Theory and Practice","author":"M Vandevelde","year":"2012","edition":"1"},{"issue":"2","key":"pone.0295268.ref019","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0034-5288(95)90060-8","article-title":"Neuroimmunological studies in steroid-responsive meningitis-arteritis in dogs","volume":"58","author":"A Tipold","year":"1995","journal-title":"Res Vet Sci"},{"issue":"2\u20134","key":"pone.0295268.ref020","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.vetimm.2009.08.007","article-title":"Marked MMP-2 transcriptional up-regulation in mononuclear leukocytes invading the subarachnoidal space in aseptic suppurative Steroid-Responsive Meningitis\u2013Arteritis in dogs","volume":"133","author":"M Schwartz","year":"2010","journal-title":"Vet Immunol Immunopathol"},{"issue":"1\u20132","key":"pone.0295268.ref021","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0165-5728(98)00134-9","article-title":"Chemotactic activity and IL-8 levels in the cerebrospinal fluid in canine steroid responsive meningitis-arteriitis","volume":"89","author":"I Burgener","year":"1998","journal-title":"J Neuroimmunol"},{"key":"pone.0295268.ref022","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1746-6148-9-23","article-title":"Interleukin-6, vascular endothelial growth factor and transforming growth factor beta 1 in canine steroid responsive meningitis-arteritis","volume":"9","author":"A Maiolini","year":"2013","journal-title":"BMC Vet Res"},{"issue":"1","key":"pone.0295268.ref023","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12974-016-0784-3","article-title":"Th17-skewed immune response and cluster of differentiation 40 ligand expression in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis","volume":"14","author":"J Freundt-Revilla","year":"2017","journal-title":"J Neuroinflammation"},{"issue":"2","key":"pone.0295268.ref024","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1046\/j.1439-0442.1999.00193.x","article-title":"Lymphocyte subset distribution in steroid responsive meningitis-arteriitis in comparison to different canine encephalitides","volume":"46","author":"A Tipold","year":"1999","journal-title":"Zentralblatt f\u00fcr Veterinarmedizin Reihe A"},{"issue":"3\u20134","key":"pone.0295268.ref025","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.vetimm.2008.05.024","article-title":"Disproportionally strong increase of B cells in inflammatory cerebrospinal fluid of dogs with Steroid-responsive Meningitis-Arteritis","volume":"125","author":"M Schwartz","year":"2008","journal-title":"Vet Immunol Immunopathol"},{"key":"pone.0295268.ref026","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/1742-2094-9-226","article-title":"Toll-like receptors 4 and 9 are responsible for the maintenance of the inflammatory reaction in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis","volume":"9","author":"A Maiolini","year":"2012","journal-title":"J Neuroinflammation"},{"issue":"12","key":"pone.0295268.ref027","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20190354","article-title":"Interleukin-17-induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer","volume":"217","author":"Y Zhang","year":"2020","journal-title":"J Exp Med"},{"key":"pone.0295268.ref028","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-0716-0154-9_1","article-title":"The Role of Neutrophils in the Immune System: An Overview","volume":"2087","author":"HL Malech","year":"2020","journal-title":"Methods Mol Biol"},{"key":"pone.0295268.ref029","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-pathol-020712-164023","article-title":"The multifaceted functions of neutrophils","volume":"9","author":"TN Mayadas","year":"2014","journal-title":"Annu Rev Pathol"},{"issue":"3","key":"pone.0295268.ref030","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nri1785","article-title":"Neutrophils and immunity: challenges and opportunities","volume":"6","author":"C Nathan","year":"2006","journal-title":"Nat Rev Immunol"},{"issue":"5663","key":"pone.0295268.ref031","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil Extracellular Traps Kill Bacteria","volume":"303","author":"V Brinkmann","year":"2004","journal-title":"Science"},{"issue":"2","key":"pone.0295268.ref032","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1083\/jcb.200606027","article-title":"Novel cell death program leads to neutrophil extracellular traps","volume":"176","author":"TA Fuchs","year":"2007","journal-title":"J Cell Biol"},{"issue":"16","key":"pone.0295268.ref033","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1182\/blood-2013-04-457671","article-title":"NETosis: how vital is it?","volume":"122","author":"BG Yipp","year":"2013","journal-title":"Blood"},{"issue":"9","key":"pone.0295268.ref034","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/nm.2847","article-title":"Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo","volume":"18","author":"BG Yipp","year":"2012","journal-title":"Nat Med"},{"issue":"12","key":"pone.0295268.ref035","doi-asserted-by":"crossref","first-page":"7413","DOI":"10.4049\/jimmunol.1000675","article-title":"A Novel Mechanism of Rapid Nuclear Neutrophil Extracellular Trap Formation in Response to Staphylococcus aureus","volume":"185","author":"FH Pilsczek","year":"2010","journal-title":"J Immunol"},{"issue":"9","key":"pone.0295268.ref036","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nm.1855","article-title":"Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense","volume":"14","author":"S Yousefi","year":"2008","journal-title":"Nat Med"},{"issue":"6","key":"pone.0295268.ref037","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.4049\/jimmunol.1201719","article-title":"Neutrophil extracellular traps: double-edged swords of innate immunity","volume":"189","author":"MJ Kaplan","year":"2012","journal-title":"J Immunol"},{"issue":"3","key":"pone.0295268.ref038","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":"SK Jorch","year":"2017","journal-title":"Nat Med"},{"key":"pone.0295268.ref039","first-page":"678","article-title":"NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils","volume":"7","author":"A Mitsios","year":"2016","journal-title":"Front Immunol"},{"issue":"5\u20136","key":"pone.0295268.ref040","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1159\/000489829","article-title":"Neutrophil Extracellular Traps in the Second Decade","volume":"10","author":"V. Brinkmann","year":"2018","journal-title":"J Innate Immun"},{"issue":"73","key":"pone.0295268.ref041","first-page":"73ra20","article-title":"Netting Neutrophils Are Major Inducers of Type I IFN Production in Pediatric Systemic Lupus Erythematosus","volume":"3","author":"GS Garcia-Romo","year":"2011","journal-title":"Sci Transl Med"},{"issue":"178","key":"pone.0295268.ref042","doi-asserted-by":"crossref","first-page":"178ra40","DOI":"10.1126\/scitranslmed.3005580","article-title":"NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis","volume":"5","author":"R Khandpur","year":"2013","journal-title":"Sci Transl Med"},{"issue":"11","key":"pone.0295268.ref043","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.autrev.2017.09.012","article-title":"Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review","volume":"16","author":"KH Lee","year":"2017","journal-title":"Autoimmun Rev"},{"issue":"6","key":"pone.0295268.ref044","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nm.1959","article-title":"Netting neutrophils in autoimmune small-vessel vasculitis","volume":"15","author":"K Kessenbrock","year":"2009","journal-title":"Nat Med"},{"issue":"3","key":"pone.0295268.ref045","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.bbrc.2018.07.069","article-title":"Citrullinated Histone 3 Causes Endothelial Barrier Dysfunction","volume":"503","author":"JE Meegan","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"pone.0295268.ref046","doi-asserted-by":"crossref","DOI":"10.1111\/micc.12352","article-title":"Neutrophil-Mediated Vascular Barrier Injury: Role of Neutrophil Extracellular Traps","volume":"24","author":"JE Meegan","year":"2017","journal-title":"Microcirculation"},{"issue":"2","key":"pone.0295268.ref047","doi-asserted-by":"crossref","first-page":"e32366","DOI":"10.1371\/journal.pone.0032366","article-title":"Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: A Predominant Role of Histones","volume":"7","author":"M Saffarzadeh","year":"2012","journal-title":"PLoS One"},{"issue":"32","key":"pone.0295268.ref048","doi-asserted-by":"crossref","first-page":"13076","DOI":"10.1073\/pnas.1200419109","article-title":"Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis","volume":"109","author":"M Demers","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"14","key":"pone.0295268.ref049","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22147734","article-title":"Methylprednisolone Induces Extracellular Trap Formation and Enhances Bactericidal Effect of Canine Neutrophils","volume":"22","author":"N Steffensen","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"4","key":"pone.0295268.ref050","first-page":"855","article-title":"The glucocorticoid inhibits neutrophils formed extracellular traps (NETs) and suppresses the inflammation caused by fallopian tube staphylococcal infection","volume":"21","author":"SX Luan","year":"2017","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"pone.0295268.ref051","first-page":"60","article-title":"Dexamethasone Inhibits S. aureus-Induced Neutrophil Extracellular Pathogen-Killing Mechanism, Possibly through Toll-Like Receptor Regulation","volume":"8","author":"T Wan","year":"2017","journal-title":"Front Immunol"},{"issue":"2","key":"pone.0295268.ref052","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1083\/jcb.200806072","article-title":"Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation","volume":"184","author":"Y Wang","year":"2009","journal-title":"J Cell Biol"},{"key":"pone.0295268.ref053","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3389\/fimmu.2012.00307","article-title":"PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures","volume":"3","author":"M Leshner","year":"2012","journal-title":"Front Immunol"},{"issue":"3","key":"pone.0295268.ref054","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1007\/s12026-017-8905-3","article-title":"Validation of an enzyme-linked immunosorbent assay for the quantification of citrullinated histone H3 as a marker for neutrophil extracellular traps in human plasma","volume":"65","author":"C Th\u00e5lin","year":"2017","journal-title":"Immunol Res"},{"issue":"1","key":"pone.0295268.ref055","doi-asserted-by":"crossref","first-page":"8972","DOI":"10.1038\/s41598-017-09337-4","article-title":"CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock","volume":"7","author":"B Pan","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0295268.ref056","doi-asserted-by":"crossref","first-page":"766391","DOI":"10.3389\/fimmu.2021.766391","article-title":"Circulating CitH3 Is a Reliable Diagnostic and Prognostic Biomarker of Septic Patients in Acute Pancreatitis","volume":"12","author":"B Pan","year":"2021","journal-title":"Front Immunol"},{"issue":"2","key":"pone.0295268.ref057","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/bjh.15906","article-title":"Citrullinated histone H3, a biomarker for neutrophil extracellular trap formation, predicts the risk of mortality in patients with cancer","volume":"186","author":"E Grilz","year":"2019","journal-title":"Br J Haematol"},{"key":"pone.0295268.ref058","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13601-020-00337-8","article-title":"Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients","volume":"10","author":"P Kuczia","year":"2020","journal-title":"Clin Transl Allergy"},{"issue":"21","key":"pone.0295268.ref059","doi-asserted-by":"crossref","first-page":"9813","DOI":"10.1073\/pnas.0909927107","article-title":"Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis","volume":"107","author":"A Hakkim","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0295268.ref060","doi-asserted-by":"crossref","first-page":"149560","DOI":"10.1155\/2012\/149560","article-title":"Deoxyribonuclease Is a Potential Counter Regulator of Aberrant Neutrophil Extracellular Traps Formation after Major Trauma","volume":"2012","author":"W Meng","year":"2012","journal-title":"Mediators Inflamm"},{"issue":"2","key":"pone.0295268.ref061","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/0090-1229(92)90213-8","article-title":"Immunologic Abnormalities in Canine Juvenile Polyarteritis Syndrome: A Naturally Occurring Animal Model of Kawasaki Disease","volume":"65","author":"PJ Felsburg","year":"1992","journal-title":"Clin Immunol Immunopathol"},{"issue":"1","key":"pone.0295268.ref062","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1353\/pbm.1991.0040","article-title":"Canine pain syndrome is a model for the study of Kawasaki disease","volume":"35","author":"JC Burns","year":"1991","journal-title":"Perspect Biol Med"},{"issue":"4","key":"pone.0295268.ref063","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/jvim.12370","article-title":"Advances in Diagnostic and Treatment Modalities for Intracranial Tumors","volume":"28","author":"PJ Dickinson","year":"2014","journal-title":"J Vet Intern Med"},{"issue":"2","key":"pone.0295268.ref064","first-page":"159","article-title":"Bacterial meningoencephalomyelitis in dogs: a retrospective study of 23 cases (1990\u20131999)","volume":"16","author":"ST Radaelli","year":"2002","journal-title":"J Vet Intern Med"},{"issue":"2","key":"pone.0295268.ref065","first-page":"178","article-title":"Neuroinflammatory diseases of the central nervous system of dogs: A retrospective study of 207 cases (2008\u20132019)","volume":"63","author":"JA Elbert","year":"2022","journal-title":"Can Vet J"},{"key":"pone.0295268.ref066","doi-asserted-by":"crossref","first-page":"4604713","DOI":"10.1155\/2016\/4604713","article-title":"How Neutrophil Extracellular Traps Become Visible","volume":"2016","author":"N de Buhr","year":"2016","journal-title":"J Immunol Res"},{"issue":"1","key":"pone.0295268.ref067","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1042\/BJ20140778","article-title":"The antimicrobial peptide LL-37 facilitates the formation of neutrophil extracellular traps","volume":"464","author":"A Neumann","year":"2014","journal-title":"Biochem J"},{"key":"pone.0295268.ref068","first-page":"307","volume-title":"Methods in Molecular Biology","author":"AS Gonzalez","year":"2014"},{"key":"pone.0295268.ref069","doi-asserted-by":"crossref","first-page":"e24437","DOI":"10.7554\/eLife.24437","article-title":"Diverse stimuli engage different neutrophil extracellular trap pathways","volume":"6","author":"EF Kenny","year":"2017","journal-title":"Elife"},{"issue":"2","key":"pone.0295268.ref070","doi-asserted-by":"crossref","first-page":"e12649","DOI":"10.1111\/cmi.12649","article-title":"Neutrophil extracellular trap formation in the Streptococcus suis-infected cerebrospinal fluid compartment","volume":"19","author":"N de Buhr","year":"2017","journal-title":"Cell Microbiol"},{"issue":"15","key":"pone.0295268.ref071","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21155289","article-title":"Role of Bacterial and Host DNases on Host-Pathogen Interaction during Streptococcus suis Meningitis","volume":"21","author":"M Meurer","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pone.0295268.ref072","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/978-1-0716-0154-9_25","volume-title":"Neutrophil: Methods and Protocols. Methods in Molecular Biology","author":"N de Buhr","year":"2020"},{"issue":"2","key":"pone.0295268.ref073","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1083\/jcb.9.2.409","article-title":"Improvements in epoxy resin embedding methods","volume":"9","author":"JH Luft","year":"1961","journal-title":"J Biophys Biochem Cytol"},{"issue":"Pt 2","key":"pone.0295268.ref074","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1365-2818.1986.tb02771.x","article-title":"Post-embedding cytochemistry with gold-labelled reagents: a review","volume":"143","author":"J. Roth","year":"1986","journal-title":"J Microsc"},{"issue":"5","key":"pone.0295268.ref075","doi-asserted-by":"crossref","first-page":"e97784","DOI":"10.1371\/journal.pone.0097784","article-title":"New Aspects on the Structure of Neutrophil Extracellular Traps from Chronic Obstructive Pulmonary Disease and In Vitro Generation","volume":"9","author":"A Obermayer","year":"2014","journal-title":"PLoS One"},{"issue":"4","key":"pone.0295268.ref076","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1111\/jvim.12360","article-title":"The Impact of Demographic, Social, and Environmental Factors on the Development of Steroid-Responsive Meningitis-Arteritis (SRMA) in the United Kingdom","volume":"28","author":"JH Rose","year":"2014","journal-title":"J Vet Int Med"},{"issue":"3","key":"pone.0295268.ref077","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.201006052","article-title":"Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps","volume":"191","author":"V Papayannopoulos","year":"2010","journal-title":"J Cell Biol"},{"issue":"4","key":"pone.0295268.ref078","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nm1565","article-title":"Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood","volume":"13","author":"SR Clark","year":"2007","journal-title":"Nat Med"},{"key":"pone.0295268.ref079","doi-asserted-by":"crossref","DOI":"10.3389\/fvets.2022.863579","article-title":"Detection of Extracellular Traps in Canine Steroid-Responsive Meningitis-Arteritis","volume":"9","author":"JC Wohlsein","year":"2022","journal-title":"Front Vet Sci"},{"issue":"3","key":"pone.0295268.ref080","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1189\/jlb.3MA0916-411R","article-title":"Human blood monocytes are able to form extracellular traps","volume":"102","author":"V Granger","year":"2017","journal-title":"J Leukoc Biol"},{"key":"pone.0295268.ref081","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.3389\/fimmu.2017.02016","article-title":"Caprine Monocytes Release Extracellular Traps against Neospora caninum In Vitro","volume":"8","author":"Z Yang","year":"2017","journal-title":"Front Immunol"},{"issue":"11","key":"pone.0295268.ref082","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1007\/s00436-014-4094-3","article-title":"Besnoitia besnoiti tachyzoites induce monocyte extracellular trap formation","volume":"113","author":"T Mu\u00f1oz-Caro","year":"2014","journal-title":"Parasitol Res"},{"key":"pone.0295268.ref083","doi-asserted-by":"crossref","first-page":"594581","DOI":"10.3389\/fimmu.2020.594581","article-title":"Human CD8+ T Cells Release Extracellular Traps Co-Localized With Cytotoxic Vesicles That Are Associated With Lesion Progression and Severity in Human Leishmaniasis","volume":"11","author":"CC Koh","year":"2020","journal-title":"Front Immunol"},{"issue":"18","key":"pone.0295268.ref084","doi-asserted-by":"crossref","first-page":"8985","DOI":"10.1073\/pnas.1822013116","article-title":"DNA threads released by activated CD4(+) T lymphocytes provide autocrine costimulation","volume":"116","author":"M Costanza","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0295268.ref085","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/sji.12592","article-title":"The Lymphocytes Stimulation Induced DNA Release, a Phenomenon Similar to NETosis","volume":"86","author":"YC Rocha Arrieta","year":"2017","journal-title":"Scand J Immunol"},{"issue":"3","key":"pone.0295268.ref086","doi-asserted-by":"crossref","first-page":"E478","DOI":"10.1073\/pnas.1711950115","article-title":"Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C","volume":"115","author":"B Ingelsson","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0295268.ref087","first-page":"139","volume-title":"Visualization and Functional Evaluation of Phagocyte Extracellular Traps. Methods in Microbiology","author":"M von K\u00f6ckritz-Blickwede","year":"2010","edition":"3"},{"issue":"2","key":"pone.0295268.ref088","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/ana.24993","article-title":"Neutrophil extracellular traps in ischemic stroke thrombi","volume":"82","author":"E Laridan","year":"2017","journal-title":"Ann Neurol"},{"issue":"5","key":"pone.0295268.ref089","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.autrev.2008.02.002","article-title":"DNase 1 and systemic lupus erythematosus","volume":"7","author":"F Mart\u00ednez Valle","year":"2008","journal-title":"Autoimmun Rev"},{"issue":"2","key":"pone.0295268.ref090","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0165-2427(94)90004-3","article-title":"Intrathecal synthesis of major immunoglobulin classes in inflammatory diseases of the canine CNS","volume":"42","author":"A Tipold","year":"1994","journal-title":"Vet Immunol Immunopathol"},{"issue":"1","key":"pone.0295268.ref091","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1128\/IAI.01104-13","article-title":"Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media","volume":"82","author":"KR Short","year":"2014","journal-title":"Infect Immun"},{"issue":"(27","key":"pone.0295268.ref092","article-title":"IgA potentiates NETosis in response to viral infection","volume":"118","author":"HD Stacey","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0295268.ref093","doi-asserted-by":"crossref","first-page":"761816","DOI":"10.3389\/fimmu.2021.761816","article-title":"IgA Complexes Induce Neutrophil Extracellular Trap Formation More Potently Than IgG Complexes","volume":"12","author":"AK Gimpel","year":"2021","journal-title":"Front Immunol"},{"key":"pone.0295268.ref094","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3389\/fimmu.2012.00428","article-title":"NETs: the missing link between cell death and systemic autoimmune diseases?","volume":"3","author":"E Darrah","year":"2013","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0295268.ref095","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1055\/a-1069-6795","article-title":"Steroid-responsive meningitis-arteritis in dogs in Germany: Are there epidemiological or clinical factors influencing recurrence rate?","volume":"48","author":"E Hilpert","year":"2020","journal-title":"Tierarztliche Praxis Ausgabe K Kleintiere Heimtiere"},{"issue":"4","key":"pone.0295268.ref096","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1111\/jvim.15543","article-title":"Clinical characteristics, breed differences, and quality of life in North American dogs with acute steroid-responsive meningitis-arteritis","volume":"33","author":"J Lau","year":"2019","journal-title":"J Vet Int Med"},{"issue":"2","key":"pone.0295268.ref097","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/jsap.12418","article-title":"Relapses in dogs with steroid-responsive meningitis-arteritis","volume":"57","author":"E Biedermann","year":"2016","journal-title":"J Small Anim Pract"},{"issue":"2","key":"pone.0295268.ref098","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1748-5827.2011.01024.x","article-title":"Immunomodulatory drugs and their application to the management of canine immune-mediated disease","volume":"52","author":"NT Whitley","year":"2011","journal-title":"J Small Anim Pract"},{"issue":"4","key":"pone.0295268.ref099","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3390\/cells9040915","article-title":"Neutrophil Extracellular Traps (NETs) Take the Central Stage in Driving Autoimmune Responses","volume":"9","author":"E Fousert","year":"2020","journal-title":"Cells"},{"issue":"6367","key":"pone.0295268.ref100","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1126\/science.aam8897","article-title":"Host DNases prevent vascular occlusion by neutrophil extracellular traps","volume":"358","author":"M Jim\u00e9nez-Alc\u00e1zar","year":"2017","journal-title":"Science"},{"key":"pone.0295268.ref101","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3389\/fimmu.2016.00236","article-title":"The Emerging Role of NETs in Venous Thrombosis and Immunothrombosis","volume":"7","author":"AS Kimball","year":"2016","journal-title":"Front Immunol"},{"issue":"9","key":"pone.0295268.ref102","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1080\/08035250600752466","article-title":"Effect of aerosolized rhDNase (Pulmozyme) on pulmonary colonization in patients with cystic fibrosis","volume":"95","author":"B Frederiksen","year":"2006","journal-title":"Acta Paediatr"},{"key":"pone.0295268.ref103","first-page":"1","article-title":"Impaired Degradation of Neutrophil Extracellular Traps: A Possible Severity Factor of Elderly Male COVID-19 Patients","volume":"12","author":"N de Buhr","year":"2022","journal-title":"J Innate Immun"},{"key":"pone.0295268.ref104","doi-asserted-by":"crossref","first-page":"100689","DOI":"10.1016\/j.nmni.2020.100689","article-title":"Consideration of dornase alfa for the treatment of severe COVID-19 acute respiratory distress syndrome","volume":"35","author":"AP Earhart","year":"2020","journal-title":"New Microbes New Infect"},{"issue":"11","key":"pone.0295268.ref105","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1038\/s41418-021-00805-z","article-title":"Patients with COVID-19: in the dark-NETs of neutrophils","volume":"28","author":"M Ackermann","year":"2021","journal-title":"Cell Death Differ"},{"issue":"1","key":"pone.0295268.ref106","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/imm.13423","article-title":"Neutrophil and remnant clearance in immunity and inflammation","volume":"165","author":"A Singhal","year":"2022","journal-title":"Immunology"},{"key":"pone.0295268.ref107","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.3389\/fimmu.2019.02957","article-title":"Citrullinated Histone H3 as a Therapeutic Target for Endotoxic Shock in Mice","volume":"10","author":"Q Deng","year":"2020","journal-title":"Front Immunol"},{"issue":"3","key":"pone.0295268.ref108","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nchembio.1735","article-title":"Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation","volume":"11","author":"HD Lewis","year":"2015","journal-title":"Nat Chem Biol"},{"issue":"7","key":"pone.0295268.ref109","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1172\/JCI67390","article-title":"Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus","volume":"123","author":"JS Knight","year":"2013","journal-title":"J Clin Invest"},{"issue":"7","key":"pone.0295268.ref110","doi-asserted-by":"crossref","first-page":"4396","DOI":"10.4049\/jimmunol.1001620","article-title":"N-\u03b1-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide, a protein arginine deiminase inhibitor, reduces the severity of murine collagen-induced arthritis","volume":"186","author":"VC Willis","year":"2011","journal-title":"J Immunol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0295268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T18:36:00Z","timestamp":1705689360000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0295268"}},"subtitle":[],"editor":[{"given":"Peter R.","family":"Corridon","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,19]]},"references-count":110,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0295268","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2024,1,19]]}}}