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Cells2019; 8(12); doi: 10.3390/cells8121528

Neutrophil Extracellular Traps in the Pathogenesis of Equine Recurrent Uveitis (ERU).

Abstract: Equine recurrent uveitis (ERU) is considered one of the most important eye diseases in horses and typically appears with relapsing inflammatory episodes without systemic effects. Various disorders have been described as an initial trigger, including infections. Independent of the initiating cause, there are numerous indications that ERU is an immune-mediated disease. We investigated whether neutrophil extracellular traps (NETs) are part of the ERU pathogenesis. Therefore, vitreous body fluids (VBF), sera, and histological sections of the eye from ERU-diseased horses were analyzed for the presence of NET markers and compared with horses with healthy eyes. In addition, NET formation by blood derived neutrophils was investigated in the presence of VBF derived from horses with healthy eyes versus ERU-diseased horses using immunofluorescence microscopy. Interestingly, NET markers like free DNA, histone-complexes, and myeloperoxidase were detected in higher amounts in samples from ERU-diseased horses. Furthermore, in vitro NET formation was higher in neutrophils incubated with VBF from diseased horses compared with those animals with healthy eyes. Finally, we characterized the ability of equine cathelicidins to induce NETs, as potential NET inducing factors in ERU-diseased horses. In summary, our findings lead to the hypothesis that ERU-diseased horses develop more NETs and that these may contribute to the pathogenesis of ERU.
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Publication Date: 2019-11-27 PubMed ID: 31783639PubMed Central: PMC6953072DOI: 10.3390/cells8121528Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study focuses on understanding the role of Neutrophil Extracellular Traps (NETs) in the pathogenesis of Equine Recurrent Uveitis (ERU), an eye disease common in horses. Comparisons were made between ERU-diseased horses and healthy ones, with noticeable increases in NET markers such as free DNA, histone-complexes, and myeloperoxidase in the former.

Introduction

  • The research focuses on Equine Recurrent Uveitis (ERU), a common eye ailment in horses characterized by repeated inflammatory episodes. The disease is often triggered by a variety of disorders, including infections.
  • While ERU appears to have no systemic effects, there’s plenty of evidence suggesting that it’s an immune-mediated disease. The research therefore aimed to investigate whether Neutrophil Extracellular Traps (NETs) contribute to the pathogenesis of ERU.

Methodology

  • The researchers analyzed vitreous body fluids (VBF), sera, and histological sections of the eye from ERU-diseased horses. They specifically looked for the presence of NET markers and compared the findings with those from horses with healthy eyes.
  • They also studied NET formation by neutrophils in the presence of VBF from both ERU-diseased horses and healthy ones using immunofluorescence microscopy.
  • In addition, they explored the ability of equine cathelicidins to induce NETs, as these could potentially act as NET inducing factors in ERU-diseased horses.

Results

  • NET markers such as free DNA, histone-complexes, and myeloperoxidase were found in higher amounts in samples from ERU-diseased horses compared to those with healthy eyes.
  • Also, in vitro NET formation was higher in neutrophils incubated with VBF from ERU-diseased horses compared to those from horses with healthy eyes.

Conclusion

  • The results of the study led researchers to propose that ERU-diseased horses produce more NETs, thereby suggesting that these might play a role in the progression of ERU. However, it’s a hypothesis that needs further investigation and validation before drawing absolute conclusions.

Cite This Article

APA
Fingerhut L, Ohnesorge B, von Borstel M, Schumski A, Strutzberg-Minder K, Mörgelin M, Deeg CA, Haagsman HP, Beineke A, von Köckritz-Blickwede M, de Buhr N. (2019). Neutrophil Extracellular Traps in the Pathogenesis of Equine Recurrent Uveitis (ERU). Cells, 8(12). https://doi.org/10.3390/cells8121528

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 8
Issue: 12

Researcher Affiliations

Fingerhut, Leonie
  • Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
  • Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
  • Clinic for Horses, University of Veterinary Medicine Hannover, Bünteweg 9, D-30559 Hannover, Germany.
Ohnesorge, Bernhard
  • Clinic for Horses, University of Veterinary Medicine Hannover, Bünteweg 9, D-30559 Hannover, Germany.
von Borstel, Myriam
  • Tierärztliche Gemeinschaftspraxis für Pferde Wedemark, Lange Loh 15, D-30900 Wedemark, Germany.
Schumski, Ariane
  • Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
Strutzberg-Minder, Katrin
  • IVD Gesellschaft für Innovative Veterinärdiagnostik mbH (IVD GmbH), Albert-Einstein-Str. 5, D-30926 Seelze, Germany.
Mörgelin, Matthias
  • Colzyx AB, Medicon Village, SE-223 81 Lund, Sweden.
Deeg, Cornelia A
  • Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Lena Christ Str. 48, D-82152 Martinsried, Germany.
Haagsman, Henk P
  • Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
Beineke, Andreas
  • Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
von Köckritz-Blickwede, Maren
  • Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
  • Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
de Buhr, Nicole
  • Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
  • Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.

MeSH Terms

  • Animals
  • Antimicrobial Cationic Peptides / immunology
  • Chronic Disease / veterinary
  • Extracellular Traps / immunology
  • Horses / immunology
  • Uveitis / immunology
  • Uveitis / veterinary
  • Vitreous Body / immunology
  • Vitreous Body / pathology
  • Cathelicidins

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

This article includes 71 references
  1. Schwink KL. Equine Uveitis. Vet. Clin. North Am. Equine Pract. 1992;8:557–574.
    doi: 10.1016/S0749-0739(17)30441-8pubmed: 1458329google scholar: lookup
  2. Lowe RC. Equine uveitis: A UK perspective. Equine Vet. J. 2010;42:46–49.
    doi: 10.1111/j.2042-3306.2010.tb05634.xpubmed: 20939166google scholar: lookup
  3. Gilger B.C., Deeg C. In: Equine Ophthalmology. 2nd ed. Gilger B.C., editor. Elsevier; Saint Louis, MO, USA: 2011.
  4. Szemes P, Gerhards H. Untersuchungen zur Prävalenz der equinen rezidivierenden Uveitis im Großraum Köln-Bonn. Prakt Tierarzt 2000;81:408–420.
  5. Gerhards H, Wollanke B. Diagnosis and therapy of uveitis in horses. Pferdeheilkd. Equine Med. 2001;17:319–329.
    doi: 10.21836/PEM20010402google scholar: lookup
  6. Von Borstel M, Oppen V, Frühauf G, Boevé D, Ohnesorge B. Langzeitergebnisse der Pars-plana-Vitrektomie bei equiner rezidivierender Uveitis. Pferdeheilkunde 2005;21:13–18.
    doi: 10.21836/PEM20050102google scholar: lookup
  7. Gilger BC. Equine recurrent uveitis: The viewpoint from the USA. Equine Vet. J. Suppl. 2010;37:57–61.
    doi: 10.1111/j.2042-3306.2010.tb05636.xpubmed: 20939168google scholar: lookup
  8. Deeg CA, Kaspers B, Gerhards H, Thurau SR, Wollanke B, Wildner G. Immune responses to retinal autoantigens and peptides in equine recurrent uveitis. Investig. Ophthalmol. Vis. Sci. 2001;42:393–398.
    pubmed: 11157872
  9. Zipplies JK, Hauck SM, Eberhardt C, Hirmer S, Amann B, Stangassinger M, Ueffing M, Deeg CA. Miscellaneous vitreous-derived IgM antibodies target numerous retinal proteins in equine recurrent uveitis. Vet. Ophthalmol. 2012;15:57–64.
    doi: 10.1111/j.1463-5224.2012.01010.xpubmed: 22432720google scholar: lookup
  10. Regan DP, Aarnio MC, Davis WS, Carmichael KP, Vandenplas ML, Lauderdale JD, Moore PA. Characterization of cytokines associated with Th17 cells in the eyes of horses with recurrent uveitis. Vet. Ophthalmol. 2012;15:145–152.
    doi: 10.1111/j.1463-5224.2011.00951.xpubmed: 22051225google scholar: lookup
  11. Kulbrock M, Lehner S, Metzger J, Ohnesorge B, Distl O. A Genome-Wide Association Study Identifies Risk Loci to Equine Recurrent Uveitis in German Warmblood Horses. PLoS ONE 2013;8:e71619.
    doi: 10.1371/journal.pone.0071619pmc: PMC3743750pubmed: 23977091google scholar: lookup
  12. Kulbrock M, von Borstel M, Rohn K, Distl O, Ohnesorge B. Occurrence and severity of equine recurrent uveitis in warmblood horses - A comparative study. Pferdeheilkd. Equine Med. 2016;29:27–36.
    doi: 10.21836/PEM20130105google scholar: lookup
  13. Dorrego-Keiter E, Tóth J, Dikker L, Sielhorst J, Schusser GF. Ritz Kultureller Nachweis von Leptospiren in Glaskörperflüssigkeit und Antikörpernachweis gegen Leptospiren in Glaskörperflüssigkeit und Serum von 225 Pferden mit equiner rezidivierender Uveitis (ERU). Berl. Munch. Tierarztl. Wochenschr. 2016;129:209–215.
    pubmed: 27344913
  14. Von Borstel M, Oey L, Strutzberg-Minder K, Boeve MH, Ohnesorge B. Direct and indirect detection of leptospires in vitreal samples of horses with ERU. Pferdeheilkd. Equine Med. 2010;26:219–225.
    doi: 10.21836/PEM20100217google scholar: lookup
  15. Vincent AT, Schiettekatte O, Goarant C, Neela VK, Bernet E, Thibeaux R, Ismail N, Mohd Khalid MKN, Amran F, Masuzawa T. Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics. PLoS Negl. Trop. Dis. 2019;13:e0007270.
    doi: 10.1371/journal.pntd.0007270pmc: PMC6532842pubmed: 31120895google scholar: lookup
  16. Kulbrock M, Distl O, Ohnesorge B. A Review of Candidate Genes for Development of Equine Recurrent Uveitis. J. Equine Vet. Sci. 2013;33:885–892.
    doi: 10.1016/j.jevs.2013.01.005google scholar: lookup
  17. Pieterse E, van der Vlag J. Breaking Immunological Tolerance in Systemic Lupus Erythematosus. Front. Immunol. 2014;5:1–8.
    doi: 10.3389/fimmu.2014.00164pmc: PMC3988363pubmed: 24782867google scholar: lookup
  18. Hakkim A, Furnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V, Herrmann M, Voll RE, Zychlinsky A. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc. Natl. Acad. Sci. USA 2010;107:9813–9818.
    doi: 10.1073/pnas.0909927107pmc: PMC2906830pubmed: 20439745google scholar: lookup
  19. De Buhr N, von Köckritz-Blickwede M. How Neutrophil Extracellular Traps Become Visible. J. Immunol. Res. 2016;2016:4604713.
    doi: 10.1155/2016/4604713pmc: PMC4884809pubmed: 27294157google scholar: lookup
  20. Steinberg BE, Grinstein S. Unconventional Roles of the NADPH Oxidase: Signaling, Ion Homeostasis, and Cell Death. Sci. STKE 2007;2007:pe11.
    doi: 10.1126/stke.3792007pe11pubmed: 17392241google scholar: lookup
  21. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science 2004;303:1532–1535.
    doi: 10.1126/science.1092385pubmed: 15001782google scholar: lookup
  22. Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J. Cell Biol. 2007;176:231–241.
    doi: 10.1083/jcb.200606027pmc: PMC2063942pubmed: 17210947google scholar: lookup
  23. Pilsczek FH, Salina D, Poon KKH, Fahey C, Yipp BG, Sibley CD, Robbins SM, Green FHY, Surette MG, Sugai M. A Novel Mechanism of Rapid Nuclear Neutrophil Extracellular Trap Formation in Response to Staphylococcus aureus. J. Immunol. 2010;185:7413–7425.
    doi: 10.4049/jimmunol.1000675pubmed: 21098229google scholar: lookup
  24. Yousefi S, Mihalache C, Kozlowski E, Schmid I, Simon HU. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ. 2009;16:1438–1444.
    doi: 10.1038/cdd.2009.96pubmed: 19609275google scholar: lookup
  25. Yipp BG, Petri B, Salina D, Jenne CN, Scott BNV, Zbytnuik LD, Pittman K, Asaduzzaman M, Wu K, Meijndert HC. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat. Med. 2012;18:1386–1393.
    doi: 10.1038/nm.2847pmc: PMC4529131pubmed: 22922410google scholar: lookup
  26. Sonawane S, Khanolkar V, Namavari A, Chaudhary S, Gandhi S, Tibrewal S, Jassim SH, Shaheen B, Hallak J, Horner JH. Ocular surface extracellular DNA and nuclease activity imbalance: A new paradigm for inflammation in dry eye disease. Investig. Ophthalmol. Vis. Sci. 2012;53:8253–8263.
    doi: 10.1167/iovs.12-10430pmc: PMC3525138pubmed: 23169882google scholar: lookup
  27. Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, Gizinski A, Yalavarthi S, Knight JS, Friday S, Li S, Patel RM, Subramanian V. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci. Transl. Med. 2013;5:1–24.
    doi: 10.1126/scitranslmed.3005580pmc: PMC3727661pubmed: 23536012google scholar: lookup
  28. Giaglis S, Hahn S, Hasler P. “The NET Outcome”: Are Neutrophil Extracellular Traps of Any Relevance to the Pathophysiology of Autoimmune Disorders in Childhood?. Front. Pediatr. 2016;4:1–8.
    doi: 10.3389/fped.2016.00097pmc: PMC5020135pubmed: 27679792google scholar: lookup
  29. Thanabalasuriar A, Scott BNV, Peiseler M, Willson ME, Zeng Z, Warrener P, Keller AE, Surewaard BGJ, Dozier EA, Korhonen JT. Neutrophil Extracellular Traps Confine Pseudomonas aeruginosa Ocular Biofilms and Restrict Brain Invasion. Cell Host Microbe 2019;25:526–536.
    doi: 10.1016/j.chom.2019.02.007pmc: PMC7364305pubmed: 30930127google scholar: lookup
  30. An S, Raju I, Surenkhuu B, Kwon JE, Gulati S, Karaman M, Pradeep A, Sinha S, Mun C, Jain S. Neutrophil extracellular traps (NETs) contribute to pathological changes of ocular graft-vs.-host disease (oGVHD) dry eye: Implications for novel biomarkers and therapeutic strategies. Ocul. Surf. 2019;17:589–614.
    doi: 10.1016/j.jtos.2019.03.010pmc: PMC6721977pubmed: 30965123google scholar: lookup
  31. Barliya T, Dardik R, Nisgav Y, Dachbash M, Gaton D, Kenet G, Ehrlich R, Weinberger D, Livnat T. Possible involvement of NETosis in inflammatory processes in the eye: Evidence from a small cohort of patients. Mol. Vis. 2017;23:922–932.
    pmc: PMC5741378pubmed: 29296072
  32. Wang L, Zhou X, Yin Y, Mai Y, Wang D, Zhang X. Hyperglycemia Induces Neutrophil Extracellular Traps Formation Through an NADPH Oxidase-Dependent Pathway in Diabetic Retinopathy. Front. Immunol. 2019;9:1–14.
    doi: 10.3389/fimmu.2018.03076pmc: PMC6331470pubmed: 30671057google scholar: lookup
  33. Kolls JK, McCray PB, Chan YR. Cytokine-mediated regulation of antimicrobial proteins. Nat. Rev. Immunol. 2008;8:829–835.
    doi: 10.1038/nri2433pmc: PMC2901862pubmed: 18949018google scholar: lookup
  34. Chi W, Yang P, Li B, Wu C, Jin H, Zhu X, Chen L, Zhou H, Huang X, Kijlstra A. IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease. J. Allergy Clin. Immunol. 2007;119:1218–1224.
    doi: 10.1016/j.jaci.2007.01.010pubmed: 17335887google scholar: lookup
  35. Chen X, Takai T, Xie Y, Niyonsaba F, Okumura K, Ogawa H. Human antimicrobial peptide LL-37 modulates proinflammatory responses induced by cytokine milieus and double-stranded RNA in human keratinocytes. Biochem. Biophys. Res. Commun. 2013;433:532–537.
    doi: 10.1016/j.bbrc.2013.03.024pubmed: 23524263google scholar: lookup
  36. Skerlavaj B, Scocchi M, Gennaro R, Risso A, Zanetti M. Structural and Functional Analysis of Horse Cathelicidin Peptides. Antimicrob. Agents Chemother. 2001;45:715–722.
    doi: 10.1128/AAC.45.3.715-722.2001pmc: PMC90362pubmed: 11181349google scholar: lookup
  37. Baake EIA, von Borstel M, Rohn K, Boevé MOB. Long-term ophthalmologic examinations of eyes with equine recurrent uveitis after pars plana vitrectomy. Pferdeheilkd. Equine Med. 2019;35:220–233.
    doi: 10.21836/PEM20190303google scholar: lookup
  38. Coorens M, Scheenstra MR, Veldhuizen EJA, Haagsman HP. Interspecies cathelicidin comparison reveals divergence in antimicrobial activity, TLR modulation, chemokine induction and regulation of phagocytosis. Sci. Rep. 2017;7:40874.
    doi: 10.1038/srep40874pmc: PMC5244392pubmed: 28102367google scholar: lookup
  39. De Buhr N, Bonilla MC, Pfeiffer J, Akhdar S, Schwennen C, Kahl BC, Waldmann K, Valentin-Weigand P, Hennig-Pauka I, von Köckritz-Blickwede M. Degraded neutrophil extracellular traps promote the growth of Actinobacillus pleuropneumoniae. Cell Death Dis. 2019;10:657.
    doi: 10.1038/s41419-019-1895-4pmc: PMC6736959pubmed: 31506432google scholar: lookup
  40. Stirling JW, Graff PS. Antigen unmasking for immunoelectron microscopy: Labeling is improved by treating with sodium ethoxide or sodium metaperiodate, then heating on retrieval medium. J. Histochem. Cytochem. 1995;43:115–123.
    doi: 10.1177/43.2.7529784pubmed: 7529784google scholar: lookup
  41. Roth J. Post-embedding cytochemistry with gold-labelled reagents: A review. J. Microsc. 1986;143:125–137.
    doi: 10.1111/j.1365-2818.1986.tb02771.xpubmed: 3531523google scholar: lookup
  42. Aucamp J, Bronkhorst AJ, Badenhorst CPS, Pretorius PJ. The diverse origins of circulating cell-free DNA in the human body: A critical re-evaluation of the literature. Biol. Rev. 2018;93:1649–1683.
    doi: 10.1111/brv.12413pubmed: 29654714google scholar: lookup
  43. Butt AN, Swaminathan R. Overview of Circulating Nucleic Acids in Plasma/Serum. Ann. N. Y. Acad. Sci. 2008;1137:236–242.
    doi: 10.1196/annals.1448.002pubmed: 18837954google scholar: lookup
  44. Wang C, Wang Y, Shi X, Tang X, Cheng W, Wang X, An Y, Li S, Xu H, Li Y. The TRAPs From Microglial Vesicles Protect Against Listeria Infection in the CNS. Front. Cell. Neurosci. 2019;13:1–17.
    doi: 10.3389/fncel.2019.00199pmc: PMC6516055pubmed: 31133815google scholar: lookup
  45. Neumann A, Berends ETM, Nerlich A, Molhoek EM, Gallo RL, Meerloo T, Nizet V, Naim HY, von Köckritz-Blickwede M. The antimicrobial peptide LL-37 facilitates the formation of neutrophil extracellular traps. Biochem. J. 2014;464:3–11.
    doi: 10.1042/BJ20140778pubmed: 25181554google scholar: lookup
  46. Labelle P. The Eye. 2017. pp. 1265–1318.
  47. Gilger BC, Malok E, Cutter KV, Stewart T, Horohov DW, Allen JB. Characterization of T-lymphocytes in the anterior uvea of eyes with chronic equine recurrent uveitis. Vet. Immunol. Immunopathol. 1999;71:17–28.
    doi: 10.1016/S0165-2427(99)00082-3pubmed: 10522783google scholar: lookup
  48. Brandes K, Wollanke B, Niedermaier G, Brem S, Gerhards H. ERU vitreal examination with ultrastructural detection of leptospira. J. Vet. Med. 2007;275:270–275.
    doi: 10.1111/j.1439-0442.2007.00921.xpubmed: 17523963google scholar: lookup
  49. Lee KH, Cavanaugh L, Leung H, Yan F, Ahmadi Z, Chong BH, Passam F. Quantification of NETs-associated markers by flow cytometry and serum assays in patients with thrombosis and sepsis. Int. J. Lab. Hematol. 2018;40:392–399.
    doi: 10.1111/ijlh.12800pubmed: 29520957google scholar: lookup
  50. Grilz E, Mauracher LM, Posch F, Königsbrügge O, Zöchbauer-Müller S, Marosi C, Lang I, Pabinger I, Ay C. Citrullinated histone H3, a biomarker for neutrophil extracellular trap formation, predicts the risk of mortality in patients with cancer. Br. J. Haematol. 2019;186:311–320.
    pmc: PMC6618331pubmed: 30968400
  51. Vallés J, Lago A, Santos MT, Latorre AM, Tembl JI, Salom JB, Nieves C, Moscardó A. Neutrophil extracellular traps are increased in patients with acute ischemic stroke: Prognostic significance. Thromb. Haemost. 2017;117:1919–1929.
    doi: 10.1160/TH17-02-0130pubmed: 28837206google scholar: lookup
  52. Sørensen OE, Borregaard N. Neutrophil extracellular traps—The dark side of neutrophils. J. Clin. Investig. 2016;126:1612–1620.
    doi: 10.1172/JCI84538pmc: PMC4855925pubmed: 27135878google scholar: lookup
  53. Gray R, McCullagh B, McCray P. NETs and CF Lung Disease: Current Status and Future Prospects. Antibiotics 2015;4:62–75.
    doi: 10.3390/antibiotics4010062pmc: PMC4790323pubmed: 27025615google scholar: lookup
  54. Neumann A, Völlger L, Berends ETM, Molhoek EM, Stapels DAC, Midon M, Friães A, Pingoud A, Rooijakkers SHM, Gallo RL. Novel Role of the Antimicrobial Peptide LL-37 in the Protection of Neutrophil Extracellular Traps against Degradation by Bacterial Nucleases. J. Innate Immun. 2014;6:860–868.
    doi: 10.1159/000363699pmc: PMC4201878pubmed: 25012862google scholar: lookup
  55. Doring Y, Manthey HD, Drechsler M, Lievens D, Megens RT, Soehnlein O, Busch M, Manca M, Koenen RR, Pelisek J. Auto-Antigenic Protein-DNA Complexes Stimulate Plasmacytoid Dendritic Cells to Promote Atherosclerosis. Circulation 2012;125:1673–1683.
    doi: 10.1161/CIRCULATIONAHA.111.046755pubmed: 22388324google scholar: lookup
  56. Reinholz M, Ruzicka T, Schauber J. Cathelicidin LL-37: An Antimicrobial Peptide with a Role in Inflammatory Skin Disease. Ann. Dermatol. 2012;24:126–135.
    doi: 10.5021/ad.2012.24.2.126pmc: PMC3346901pubmed: 22577261google scholar: lookup
  57. Bruhn O, Grötzinger J, Cascorbi I, Jung S. Antimicrobial peptides and proteins of the horse—Insights into a well-armed organism. Vet. Res. 2011;42:1–22.
    doi: 10.1186/1297-9716-42-98pmc: PMC3179947pubmed: 21888650google scholar: lookup
  58. Scocchi M, Bontempo D, Boscolo S, Tomasinsig L, Giulotto E, Zanetti M. Novel cathelicidins in horse leukocytes. FEBS Lett. 1999;457:459–464.
    doi: 10.1016/S0014-5793(99)01097-2pubmed: 10471829google scholar: lookup
  59. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007;449:564–569.
    doi: 10.1038/nature06116pubmed: 17873860google scholar: lookup
  60. McLaughlin BG, McLaughlin PS. Equine vitreous humor chemical concentrations: Correlation with serum concentrations, and postmortem changes with time and temperature. Can. J. Vet. Res. 1988;52:476–480.
    pmc: PMC1255494pubmed: 3196976
  61. Johansson J, Gudmonsson GH, Rottenberg ME, Berndt K, Agerberth B. Conformation-dependent Antibacterial Activity of the Naturally Occurring Human Peptide LL-37. J. Biol. Chem. 1998;273:3718–3724.
    doi: 10.1074/jbc.273.6.3718pubmed: 9452503google scholar: lookup
  62. Kościuczuk EM, Lisowski P, Jarczak J, Strzałkowska N, Jóźwik A, Horbańczuk J, Krzyzewski J, Zwierzchowski L, Bagnicka E. Cathelicidins: Family of antimicrobial peptides. A review. Mol. Biol. Rep. 2012;39:10957–10970.
    doi: 10.1007/s11033-012-1997-xpmc: PMC3487008pubmed: 23065264google scholar: lookup
  63. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DYM. Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis. N. Engl. J. Med. 2002;347:1151–1160.
    doi: 10.1056/NEJMoa021481pubmed: 12374875google scholar: lookup
  64. Scharrig E, Carestia A, Ferrer MF, Cédola M, Pretre G, Drut R, Picardeau M, Schattner M, Gómez RM. Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira. PLoS Negl. Trop. Dis. 2015;9:e0003927.
    doi: 10.1371/journal.pntd.0003927pmc: PMC4498591pubmed: 26161745google scholar: lookup
  65. Wilson-Welder JH, Frank AT, Hornsby RL, Olsen SC, Alt DP. Interaction of bovine peripheral blood polymorphonuclear cells and Leptospira species; innate responses in the natural bovine reservoir host. Front. Microbiol. 2016;7:1–14.
    doi: 10.3389/fmicb.2016.01110pmc: PMC4949235pubmed: 27486445google scholar: lookup
  66. Tömördy E, Hässig M, Spiess BM. The outcome of pars plana vitrectomy in horses with equine recurrent uveitis with regard to the presence or absence of intravitreal antibodies against various serovars of Leptospira interrogans. Pferdeheilkunde 2010;26:251–254.
    doi: 10.21836/PEM20100222google scholar: lookup
  67. Mun C, Gulati S, Tibrewal S, Chen YF, An S, Surenkhuu B, Raju I, Buwick M, Ahn A, Kwon JE. A Phase I/II Placebo-Controlled Randomized Pilot Clinical Trial of Recombinant Deoxyribonuclease (DNase) Eye Drops Use in Patients with Dry Eye Disease. Transl. Vis. Sci. Technol. 2019;8:10.
    doi: 10.1167/tvst.8.3.10pmc: PMC6504128pubmed: 31110911google scholar: lookup
  68. Tibrewal S, Sarkar J, Jassim SH, Gandhi S, Sonawane S, Chaudhary S, Byun YS, Ivanir Y, Hallak J, Horner JH. Tear fluid extracellular dna: Diagnostic and therapeutic implications in dry eye disease. Investig. Ophthalmol. Vis. Sci. 2013;54:8051–8061.
    doi: 10.1167/iovs.13-12844pmc: PMC3860379pubmed: 24255046google scholar: lookup
  69. Mannermaa E, Reinisalo M, Ranta VP, Vellonen KS, Kokki H, Saarikko A, Kaarniranta K, Urtti A. Filter-cultured ARPE-19 cells as outer blood–retinal barrier model. Eur. J. Pharm. Sci. 2010;40:289–296.
    doi: 10.1016/j.ejps.2010.04.001pubmed: 20385230google scholar: lookup
  70. Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, Lohmeyer J, Preissner KT. Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: A Predominant Role of Histones. PLoS ONE 2012;7:e32366.
    doi: 10.1371/journal.pone.0032366pmc: PMC3289648pubmed: 22389696google scholar: lookup
  71. Estúa-Acosta GA, Zamora-Ortiz R, Buentello-Volante B, García-Mejía M, Garfias Y. Neutrophil Extracellular Traps: Current Perspectives in the Eye. Cells 2019;8:979.
    doi: 10.3390/cells8090979pmc: PMC6769795pubmed: 31461831google scholar: lookup

Citations

This article has been cited 23 times.
  1. Cooper BL, Hobbs KJ, Bayless R, Stinson-Miller A, Gruber E, Hepworth-Warren K, Lavoie JP, Sheats MK. A Portable Fluorometer Detects Significantly Elevated Cell-Free DNA in Tracheal Wash and Bronchoalveolar Lavage Fluid in Horses with Severe Asthma. Animals (Basel) 2025 Dec 3;15(23).
    doi: 10.3390/ani15233483pubmed: 41375541google scholar: lookup
  2. Sprenzel CJ, Amann B, Deeg CA, Degroote RL. Glycan Signatures on Neutrophils in an Equine Model for Autoimmune Uveitis. Biomolecules 2025 Oct 12;15(10).
    doi: 10.3390/biom15101444pubmed: 41154673google scholar: lookup
  3. Meiseberg LK, Mergani A, Delarocque J, Imker R, Köhn D, Wanes D, Bonilla MC, Veldhuizen EJA, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N. Equine Asthma Is Characterised by Severity-Dependent Correlations Between Blood Neutrophil Cholesterol Content and NET Formation. Eur J Immunol 2025 Oct;55(10):e70072.
    doi: 10.1002/eji.70072pubmed: 41054022google scholar: lookup
  4. Sheahan BJ, Schubert AG, Schubert W, Sheats MK, Schnabel LV, Gilbertie JM. Equine neutrophils selectively release neutrophil extracellular traps in response to chemical and bacterial agonists. Front Vet Sci 2025;12:1512343.
    doi: 10.3389/fvets.2025.1512343pubmed: 40066197google scholar: lookup
  5. Stafford LS, Plummer CE, Smith WC, Gibson DJ, Sharma J, Vicuna V, Diakite S, Larkin J 3rd. A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis. Front Immunol 2024;15:1513157.
    doi: 10.3389/fimmu.2024.1513157pubmed: 39867889google scholar: lookup
  6. Bayless RL, Cooper BL, Sheats MK. Extracted Plasma Cell-Free DNA Concentrations Are Elevated in Colic Patients with Systemic Inflammation. Vet Sci 2024 Sep 12;11(9).
    doi: 10.3390/vetsci11090427pubmed: 39330806google scholar: lookup
  7. Hobbs KJ, Cooper BL, Dembek K, Sheats MK. Investigation of Extracted Plasma Cell-Free DNA as a Biomarker in Foals with Sepsis. Vet Sci 2024 Aug 1;11(8).
    doi: 10.3390/vetsci11080346pubmed: 39195800google scholar: lookup
  8. Degroote RL, Schmalen A, Hauck SM, Deeg CA. Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis. Biomedicines 2023 Dec 20;12(1).
    doi: 10.3390/biomedicines12010019pubmed: 38275380google scholar: lookup
  9. Pilchová V, Gerhauser I, Armando F, Wirz K, Schreiner T, de Buhr N, Gabriel G, Wernike K, Hoffmann D, Beer M, Baumgärtner W, von Köckritz-Blickwede M, Schulz C. Characterization of young and aged ferrets as animal models for SARS-CoV-2 infection with focus on neutrophil extracellular traps. Front Immunol 2023;14:1283595.
    doi: 10.3389/fimmu.2023.1283595pubmed: 38169647google scholar: lookup
  10. García-Bengoa M, Meurer M, Stehr M, Elamin AA, Singh M, Oehlmann W, Mörgelin M, von Köckritz-Blickwede M. Mycobacterium tuberculosis PE/PPE proteins enhance the production of reactive oxygen species and formation of neutrophil extracellular traps. Front Immunol 2023;14:1206529.
    doi: 10.3389/fimmu.2023.1206529pubmed: 37675111google scholar: lookup
  11. Birckhead EM, Das S, Tidd N, Raidal SL, Raidal SR. Visualizing neutrophil extracellular traps in septic equine synovial and peritoneal fluid samples using immunofluorescence microscopy. J Vet Diagn Invest 2023 Nov;35(6):751-760.
    doi: 10.1177/10406387231196552pubmed: 37661696google scholar: lookup
  12. Kuschnerow P, Munder A, de Buhr N, Mörgelin M, Jirmo AC, Ackermann M, von Köckritz-Blickwede M, Tümmler B, Cramer N. Competitive survival of clonal serial Pseudomonas aeruginosa isolates from cystic fibrosis airways in human neutrophils. iScience 2023 Apr 21;26(4):106475.
    doi: 10.1016/j.isci.2023.106475pubmed: 37096049google scholar: lookup
  13. Zeng J, Wu M, Zhou Y, Zhu M, Liu X. Neutrophil Extracellular Traps (NETs) in Ocular Diseases: An Update. Biomolecules 2022 Oct 8;12(10).
    doi: 10.3390/biom12101440pubmed: 36291649google scholar: lookup
  14. Hoffmann ALC, Hauck SM, Deeg CA, Degroote RL. Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro. Int J Mol Sci 2022 Aug 23;23(17).
    doi: 10.3390/ijms23179555pubmed: 36076947google scholar: lookup
  15. Bonilla MC, Quiros ON, Wendt M, Hennig-Pauka I, Mörgelin M, von Köckritz-Blickwede M, de Buhr N. New Insights into Neutrophil Extracellular Trap (NETs) Formation from Porcine Neutrophils in Response to Bacterial Infections. Int J Mol Sci 2022 Aug 11;23(16).
    doi: 10.3390/ijms23168953pubmed: 36012224google scholar: lookup
  16. Fingerhut L, Yücel L, Strutzberg-Minder K, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N. Ex Vivo and In Vitro Analysis Identify a Detrimental Impact of Neutrophil Extracellular Traps on Eye Structures in Equine Recurrent Uveitis. Front Immunol 2022;13:830871.
    doi: 10.3389/fimmu.2022.830871pubmed: 35251020google scholar: lookup
  17. Wollanke B, Gerhards H, Ackermann K. Infectious Uveitis in Horses and New Insights in Its Leptospiral Biofilm-Related Pathogenesis. Microorganisms 2022 Feb 7;10(2).
    doi: 10.3390/microorganisms10020387pubmed: 35208842google scholar: lookup
  18. Bayless RL, Cooper BL, Sheats MK. Investigation of plasma cell-free DNA as a potential biomarker in horses. J Vet Diagn Invest 2022 May;34(3):402-406.
    doi: 10.1177/10406387221078047pubmed: 35168428google scholar: lookup
  19. Ackermann K, Kenngott R, Settles M, Gerhards H, Maierl J, Wollanke B. In Vivo Biofilm Formation of Pathogenic Leptospira spp. in the Vitreous Humor of Horses with Recurrent Uveitis. Microorganisms 2021 Sep 9;9(9).
    doi: 10.3390/microorganisms9091915pubmed: 34576809google scholar: lookup
  20. Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
    doi: 10.3389/fimmu.2020.609855pubmed: 33488614google scholar: lookup
  21. Mulay SR, Anders HJ. Neutrophils and Neutrophil Extracellular Traps Regulate Immune Responses in Health and Disease. Cells 2020 Sep 20;9(9).
    doi: 10.3390/cells9092130pubmed: 32962213google scholar: lookup
  22. Neumann A, Brogden G, von Köckritz-Blickwede M. Extracellular Traps: An Ancient Weapon of Multiple Kingdoms. Biology (Basel) 2020 Feb 18;9(2).
    doi: 10.3390/biology9020034pubmed: 32085405google scholar: lookup
  23. Degroote RL, Weigand M, Hauck SM, Deeg CA. IL8 and PMA Trigger the Regulation of Different Biological Processes in Granulocyte Activation. Front Immunol 2019;10:3064.
    doi: 10.3389/fimmu.2019.03064pubmed: 32010136google scholar: lookup
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