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Frontiers in immunology2022; 13; 921077; doi: 10.3389/fimmu.2022.921077

Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity.

Abstract: Asthma encompasses a spectrum of heterogenous immune-mediated respiratory disorders sharing a similar clinical pattern characterized by cough, wheeze and exercise intolerance. In horses, equine asthma can be subdivided into severe or moderate asthma according to clinical symptoms and the extent of airway neutrophilic inflammation. While severe asthmatic horses are characterized by an elevated neutrophilic inflammation of the lower airways, cough, dyspnea at rest and high mucus secretion, horses with moderate asthma show a milder neutrophilic inflammation, exhibit intolerance to exercise but no labored breathing at rest. Yet, the physiopathology of different phenotypes of equine asthma remains poorly understood and there is a need to elucidate the underlying mechanisms tailoring those phenotypes in order to improve clinical management and elaborate novel therapeutic strategies. In this study, we sought to quantify the presence of neutrophil extracellular traps (NETs) in bronchoalveolar lavage fluids (BALF) of moderate or severe asthmatic horses and healthy controls, and assessed whether NETs correlated with disease severity. To this end, we evaluated the amounts of NETs by measuring cell-free DNA and MPO-DNA complexes in BALF supernatants or by quantifying NETs release by BALF cells by confocal microscopy. We were able to unequivocally identify elevated NETs levels in BALF of severe asthmatic horses as compared to healthy controls or moderate asthmatic horses. Moreover, we provided evidence that BALF NETs release was a specific feature seen in severe equine asthma, as opposed to moderate asthma, and correlated with disease severity. Finally, we showed that NETs could act as a predictive factor for severe equine asthma. Our study thus uniquely identifies NETs in BALF of severe asthmatic horses using three distinct methods and supports the idea that moderate and severe equine asthma do not rely on strictly similar pathophysiological mechanisms. Our data also suggest that NETs represent a relevant biomarker, a putative driver and a potential therapeutic target in severe asthma disease.
Copyright © 2022 Janssen, Tosi, Hego, Maréchal, Marichal and Radermecker.
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Publication Date: 2022-07-13 PubMed ID: 35911691PubMed Central: PMC9326094DOI: 10.3389/fimmu.2022.921077Google Scholar: Lookup
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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.

This research looks at equine asthma and specifically the presence and potential role of neutrophil extracellular traps (NETs) in the bronchoalveolar lavage fluids (BALF) of horses with severe asthma. The authors conclude that NETs levels are elevated in severe cases, suggesting different underlying mechanisms for moderate and severe asthma, and that NETs could serve as a useful biomarker and potential therapeutic target.

Background

  • The paper starts by describing asthma as a variety of immune-mediated disorders affecting the respiratory system, symptoms of which include wheezing, exercise intolerance, and coughing.
  • Equine asthma – asthma in horses – is divided into two categories: severe and moderate, based on the degree of airway neutrophilic inflammation and clinical symptoms.
  • Severe equine asthma is marked by high neutrophilic inflammation in the lower airways, an abundance of mucus secretion, and symptoms such as labored breathing and coughing. In contrast, moderate asthma is characterized by milder inflammation and exercise intolerance, but no laborious breathing while resting.
  • Despite this categorization, the mechanisms driving the differences in these asthma phenotypes remain unclear, representing a gap in understanding which the study aims to address.

Study purpose and methods

  • The research aims to quantify the presence of Neutrophil extracellular traps (NETs) in the bronchoalveolar lavage fluid (BALF) of horses with moderate or severe asthma, as well as in healthy horses.
  • More importantly, the study aims to determine if the level of NETs correlates with the severity of the asthma.
  • To achieve this, the researchers measured cell-free DNA and MPO-DNA complexes in the BALF supernatants and assessed the release of NETs from BALF cells using confocal microscopy.

Findings

  • The research reports that there is a noticeable increase in NETs levels in the BALF of horses with severe asthma compared to healthy horses and those showing signs of moderate asthma.
  • This rise in NETs only appears in cases of severe equine asthma, indicating that it could correlate with disease severity.
  • Beyond this, the study suggests NETs could potentially be a predictive indicator of severe equine asthma.

Conclusions and suggestions for further research

  • Research here suggests that moderate and severe equine asthma has different underlying pathophysiological mechanisms.
  • With the detection of elevated NETs in the BALF of severely asthmatic horses, NETs could be seen as an important biomarker, a potential driver of the disease, and a possible target for treatment in severe asthmatic conditions.
  • However, further research is needed to confirm these observations and to expand our understanding of these NETs in the pathophysiology of equine asthma.

Cite This Article

APA
Janssen P, Tosi I, Hego A, Maréchal P, Marichal T, Radermecker C. (2022). Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity. Front Immunol, 13, 921077. https://doi.org/10.3389/fimmu.2022.921077

Publication

Frontiers in immunology
ISSN: 1664-3224
NlmUniqueID: 101560960
Country: Switzerland
Language: English
Volume: 13
Pages: 921077

Researcher Affiliations

Janssen, Pierre
  • Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
  • Faculty of Veterinary Medicine, Liège University, Liège, Belgium.
Tosi, Irene
  • Faculty of Veterinary Medicine, Liège University, Liège, Belgium.
Hego, Alexandre
  • In Vitro Imaging Platform, GIGA Institute, Liège University, Liège, Belgium.
Maréchal, Pauline
  • Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
Marichal, Thomas
  • Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
  • Faculty of Veterinary Medicine, Liège University, Liège, Belgium.
Radermecker, Coraline
  • Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
  • Faculty of Veterinary Medicine, Liège University, Liège, Belgium.

MeSH Terms

  • Animals
  • Asthma / pathology
  • Asthma / veterinary
  • Bronchoalveolar Lavage Fluid
  • Cough / pathology
  • Cough / veterinary
  • Extracellular Traps
  • Horses
  • Inflammation / pathology
  • Inflammation / veterinary
  • Neutrophils / pathology
  • Patient Acuity

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 93 references
  1. Wenzel SE. Asthma: Defining of the Persistent Adult Phenotypes. Lancet 2006 368(9537):804–13.
    doi: 10.1016/S0140-6736(06)69290-8pubmed: 16935691google scholar: lookup
  2. Holgate ST. Pathogenesis of Asthma. Clin Exp Allergy 2008 38(6):872–97.
    doi: 10.1111/j.1365-2222.2008.02971.xpubmed: 18498538google scholar: lookup
  3. Wenzel SE. Asthma Phenotypes: The Evolution From Clinical to Molecular Approaches. Nat Med 2012 18(5):716–25.
    doi: 10.1038/nm.2678pubmed: 22561835google scholar: lookup
  4. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D. Equine Asthma: Current Understanding and Future Directions. Front Vet Sci 2020 7:450.
    doi: 10.3389/fvets.2020.00450pmc: PMC7438831pubmed: 32903600google scholar: lookup
  5. Couëtil LL, Hoffman AM, Hodgson J, Buechner-Maxwell V, Viel L, Wood JLN. Inflammatory Airway Disease of Horses. J Veterinary Internal Med 2007 21(2):356–61.
    doi: 10.1111/j.1939-1676.2007.tb02975.xpubmed: 17427403google scholar: lookup
  6. Hotchkiss JW, Reid SWJ, Christley RM. A Survey of Horse Owners in Great Britain Regarding Horses in Their Care. Part 2: Risk Factors for Recurrent Airway Obstruction. Equine Veterinary J 2007 39(4):301–8.
    doi: 10.2746/042516407x180129pubmed: 17722720google scholar: lookup
  7. Bond S, Léguillette R, Richard EA, Couetil L, Lavoie J, Martin JG. Equine Asthma: Integrative Biologic Relevance of a Recently Proposed Nomenclature. J Vet Intern Med 2018 32(6):2088–98.
    doi: 10.1111/jvim.15302pmc: PMC6271326pubmed: 30294851google scholar: lookup
  8. Ivester KM, Couëtil LL, Moore GE. An Observational Study of Environmental Exposures, Airway Cytology, and Performance in Racing Thoroughbreds. J Veterinary Internal Med 2018 32(5):1754–62.
    doi: 10.1111/jvim.15226pmc: PMC6189343pubmed: 30222207google scholar: lookup
  9. Allen K, Franklin S. RAO and IAD: Respiratory Disease in Horses Revisited. Practice 2007 29(2):76–85.
    doi: 10.1136/inpract.29.2.76google scholar: lookup
  10. Davis KU, Sheats MK. Differential Gene Expression and Ingenuity Pathway Analysis of Bronchoalveolar Lavage Cells From Horses With Mild/Moderate Neutrophilic or Mastocytic Inflammation on BAL Cytology. Veterinary Immunol Immunopathol 2021 234:110195.
    doi: 10.1016/j.vetimm.2021.110195pmc: PMC8132494pubmed: 33588285google scholar: lookup
  11. Bedenice D, Mazan MR, Hoffman AM. Association Between Cough and Cytology of Bronchoalveolar Lavage Fluid and Pulmonary Function in Horses Diagnosed With Inflammatory Airway Disease. J Veterinary Internal Med 2008 22(4):1022–8.
    doi: 10.1111/j.1939-1676.2008.0109.xpubmed: 18498325google scholar: lookup
  12. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an Asthma-Like Disease of Horses. Respirology 2011 16(7):1027–46.
    doi: 10.1111/j.1440-1843.2011.02033.xpubmed: 21824219google scholar: lookup
  13. Borregaard N. Neutrophils, From Marrow to Microbes. Immunity 2010 33(5):657–70.
    doi: 10.1016/j.immuni.2010.11.011pubmed: 21094463google scholar: lookup
  14. Papayannopoulos V. Neutrophil Extracellular Traps in Immunity and Disease. Nat Rev Immunol 2018 18(2):134–47.
    doi: 10.1038/nri.2017.105pubmed: 28990587google scholar: lookup
  15. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS. Neutrophil Extracellular Traps Kill Bacteria. Science 2004 303(5663):1532–5.
    doi: 10.1126/science.1092385pubmed: 15001782google scholar: lookup
  16. Cortjens B, de Boer OJ, de Jong R, Antonis AF, Sabogal Piñeros YS, Lutter R. Neutrophil Extracellular Traps Cause Airway Obstruction During Respiratory Syncytial Virus Disease. J Pathol 2016 238(3):401–11.
    doi: 10.1002/path.4660pubmed: 26468056google scholar: lookup
  17. Radermecker C, Detrembleur N, Guiot J, Cavalier E, Henket M, d’Emal C. Neutrophil Extracellular Traps Infiltrate the Lung Airway, Interstitial, and Vascular Compartments in Severe COVID-19. J Exp Med 2020 217(12).
    doi: 10.1084/jem.20201012pmc: PMC7488867pubmed: 32926097google scholar: lookup
  18. Jenne CN, Wong CHY, Zemp FJ, McDonald B, Rahman MM, Forsyth PA. Neutrophils Recruited to Sites of Infection Protect From Virus Challenge by Releasing Neutrophil Extracellular Traps. Cell Host Microbe 2013 13(2):169–80.
    doi: 10.1016/j.chom.2013.01.005pubmed: 23414757google scholar: lookup
  19. Rochael NC, Guimarães-Costa AB, Nascimento MTC, DeSouza-Vieira TS, Oliveira MP, Garcia e Souza LF. Classical ROS-Dependent and Early/Rapid ROS-Independent Release of Neutrophil Extracellular Traps Triggered by Leishmania Parasites. Sci Rep 2015 5(1):18302.
    doi: 10.1038/srep18302pmc: PMC4682131pubmed: 26673780google scholar: lookup
  20. Denkers E, Abi Abdallah D. Neutrophils Cast Extracellular Traps in Response to Protozoan Parasites. Front Immunol 2012 3.
    doi: 10.3389/fimmu.2012.00382pmc: PMC3522045pubmed: 23248631google scholar: lookup
  21. Behnen M, Leschczyk C, Möller S, Batel T, Klinger M, Solbach W. Immobilized Immune Complexes Induce Neutrophil Extracellular Trap Release by Human Neutrophil Granulocytes via Fcγriiib and Mac-1. J Immunol 2014 193(4):1954–65.
    doi: 10.4049/jimmunol.1400478pubmed: 25024378google scholar: lookup
  22. Chatfield SM, Grebe K, Whitehead LW, Rogers KL, Nebl T, Murphy JM. Monosodium Urate Crystals Generate Nuclease-Resistant Neutrophil Extracellular Traps via a Distinct Molecular Pathway. J Immunol 2018 200(5):1802–16.
    doi: 10.4049/jimmunol.1701382pubmed: 29367211google scholar: lookup
  23. Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, Gizinski A, Yalavarthi S, Knight JS. NETs Are a Source of Citrullinated Autoantigens and Stimulate Inflammatory Responses in Rheumatoid Arthritis. Sci Trans Med 2013 5(178):178ra40.
    doi: 10.1126/scitranslmed.3005580pmc: PMC3727661pubmed: 23536012google scholar: lookup
  24. Söderberg D, Segelmark M. Neutrophil Extracellular Traps in ANCA-Associated Vasculitis. Front Immunol 2016 7.
    doi: 10.3389/fimmu.2016.00256pmc: PMC4928371pubmed: 27446086google scholar: lookup
  25. Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V. Neutrophil Extracellular Traps License Macrophages for Cytokine Production in Atherosclerosis. Science 2015 349(6245):316–20.
    doi: 10.1126/science.aaa8064pmc: PMC4854322pubmed: 26185250google scholar: lookup
  26. Gould TJ, Vu TT, Swystun LL, Dwivedi DJ, Mai SHC, Weitz JI. Neutrophil Extracellular Traps Promote Thrombin Generation Through Platelet-Dependent and Platelet-Independent Mechanisms. Arteriosclerosis Thrombosis Vasc Biol 2014 34(9):1977–84.
    doi: 10.1161/ATVBAHA.114.304114pubmed: 25012129google scholar: lookup
  27. Alhamdi Y, Toh CH. Recent Advances in Pathophysiology of Disseminated Intravascular Coagulation: The Role of Circulating Histones and Neutrophil Extracellular Traps. F1000Res 2017 6:2143.
    doi: 10.12688/f1000research.12498.1pmc: PMC5785716pubmed: 29399324google scholar: lookup
  28. Radermecker C, Sabatel C, Vanwinge C, Ruscitti C, Maréchal P, Perin F. Locally Instructed CXCR4 Hi Neutrophils Trigger Environment-Driven Allergic Asthma Through the Release of Neutrophil Extracellular Traps. Nat Immunol 2019 20(11):1444–55.
    doi: 10.1038/s41590-019-0496-9pmc: PMC6859073pubmed: 31591573google scholar: lookup
  29. Wan R, Jiang J, Hu C, Chen X, Chen C, Zhao B. Neutrophil Extracellular Traps Amplify Neutrophil Recruitment and Inflammation in Neutrophilic Asthma by Stimulating the Airway Epithelial Cells to Activate the TLR4/ NF-κb Pathway and Secrete Chemokines. Aging (Albany NY) 2020 12(17):16820–36.
    doi: 10.18632/aging.103479pmc: PMC7521522pubmed: 32756014google scholar: lookup
  30. Pedersen F, Marwitz S, Holz O, Kirsten A, Bahmer T, Waschki B. Neutrophil Extracellular Trap Formation and Extracellular DNA in Sputum of Stable COPD Patients. Respir Med 2015 109(10):1360–2.
    doi: 10.1016/j.rmed.2015.08.008pubmed: 26321138google scholar: lookup
  31. Radermecker C, Hego A, Delvenne P, Marichal T. Identification and Quantitation of Neutrophil Extracellular Traps in Human Tissue Sections. Bio-protocol 2021 11(18):e4159–9.
    doi: 10.21769/BioProtoc.4159pmc: PMC8481026pubmed: 34692909google scholar: lookup
  32. Ginley BG, Emmons T, Lutnick B, Urban CF, Segal BH, Sarder P. Computational Detection and Quantification of Human and Mouse Neutrophil Extracellular Traps in Flow Cytometry and Confocal Microscopy. Sci Rep 2017 7(1):17755.
    doi: 10.1038/s41598-017-18099-ypmc: PMC5736696pubmed: 29259241google scholar: lookup
  33. Côté O, Clark ME, Viel L, Labbé G, Seah SYK, Khan MA. Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation. PLoS One 2014 9(4):e96217.
    doi: 10.1371/journal.pone.0096217pmc: PMC4002474pubmed: 24777050google scholar: lookup
  34. Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP. Neutrophil Extracellular Traps Are Downregulated by Glucocorticosteroids in Lungs in an Equine Model of Asthma. Respir Res 2017 18(1):207.
    doi: 10.1186/s12931-017-0689-4pmc: PMC5727947pubmed: 29233147google scholar: lookup
  35. Herteman N, Vargas A, Lavoie JP. Characterization of Circulating Low-Density Neutrophils Intrinsic Properties in Healthy and Asthmatic Horses. Sci Rep 2017 7(1):7743.
    doi: 10.1038/s41598-017-08089-5pmc: PMC5552858pubmed: 28798364google scholar: lookup
  36. Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma—Current Understanding and What Is Missing. Animals 2022 12(6):744.
    doi: 10.3390/ani12060744pmc: PMC8944511pubmed: 35327141google scholar: lookup
  37. Cordeau ME, Joubert P, Dewachi O, Hamid Q, Lavoie JP. IL-4, IL-5 and IFN-Gamma mRNA Expression in Pulmonary Lymphocytes in Equine Heaves. Vet Immunol Immunopathol 2004 97(1–2):87–96.
    doi: 10.1016/j.vetimm.2003.08.013pubmed: 14700540google scholar: lookup
  38. Hansen S, Otten ND, Birch K, Skovgaard K, Hopster-Iversen C, Fjeldborg J. Bronchoalveolar Lavage Fluid Cytokine, Cytology and IgE Allergen in Horses With Equine Asthma. Veterinary Immunol Immunopathol 2020 220:109976.
    doi: 10.1016/j.vetimm.2019.109976pubmed: 31786444google scholar: lookup
  39. Debrue M, Hamilton E, Joubert P, Lajoie-Kadoch S, Lavoie JP. Chronic Exacerbation of Equine Heaves Is Associated With an Increased Expression of Interleukin-17 mRNA in Bronchoalveolar Lavage Cells. Veterinary Immunol Immunopathol 2005 105(1):25–31.
    doi: 10.1016/j.vetimm.2004.12.013pubmed: 15797472google scholar: lookup
  40. Ricciardolo FLM, Sorbello V, Folino A, Gallo F, Massaglia GM, Favatà G. Identification of IL-17f/Frequent Exacerbator Endotype in Asthma. J Allergy Clin Immunol 2017 140(2):395–406.
    doi: 10.1016/j.jaci.2016.10.034pubmed: 27931975google scholar: lookup
  41. Pacholewska A, Kraft MF, Gerber V, Jagannathan V. Differential Expression of Serum MicroRNAs Supports CD4+ T Cell Differentiation Into Th2/Th17 Cells in Severe Equine Asthma. Genes 2017 8(12):383.
    doi: 10.3390/genes8120383pmc: PMC5748701pubmed: 29231896google scholar: lookup
  42. Uberti B, Morán G. Role of Neutrophils in Equine Asthma. Anim Health Res Rev 2018 19(1):65–73.
    doi: 10.1017/S146625231800004Xpubmed: 29792391google scholar: lookup
  43. Bullone M, Joubert P, Gagné A, Lavoie JP, Hélie P. Bronchoalveolar Lavage Fluid Neutrophilia Is Associated With the Severity of Pulmonary Lesions During Equine Asthma Exacerbations. Equine Veterinary J 2018 50(5):609–15.
    doi: 10.1111/evj.12806pubmed: 29341228google scholar: lookup
  44. Brazil TJ, Dagleish MP, McGorum BC, Dixon PM, Haslett C, Chilvers ER. Kinetics of Pulmonary Neutrophil Recruitment and Clearance in a Natural and Spontaneously Resolving Model of Airway Inflammation. Clin Exp Allergy 2005 35(7):854–65.
    doi: 10.1111/j.1365-2222.2005.02231.xpubmed: 16008670google scholar: lookup
  45. Vanderstock JM, Lecours MP, Lavoie-Lamoureux A, Gottschalk M, Segura M, Lavoie JP. Phagocytosis, Bacterial Killing, and Cytokine Activation of Circulating Blood Neutrophils in Horses With Severe Equine Asthma and Control Horses. Am J Veterinary Res 2018 79(4):455–64.
    doi: 10.2460/ajvr.79.4.455pubmed: 29583047google scholar: lookup
  46. Kanamaru R, Ohzawa H, Miyato H, Yamaguchi H, Hosoya Y, Lefor AK. Neutrophil Extracellular Traps Generated by Low Density Neutrophils Obtained From Peritoneal Lavage Fluid Mediate Tumor Cell Growth and Attachment. JoVE (J Visualized Experiments) 2018 138):e58201.
    doi: 10.3791/58201pmc: PMC6126606pubmed: 30124642google scholar: lookup
  47. Kanamaru R, Ohzawa H, Miyato H, Matsumoto S, Haruta H, Kurashina K. Low Density Neutrophils (LDN) in Postoperative Abdominal Cavity Assist the Peritoneal Recurrence Through the Production of Neutrophil Extracellular Traps (NETs). Sci Rep 2018 8(1):632.
    doi: 10.1038/s41598-017-19091-2pmc: PMC5766579pubmed: 29330531google scholar: lookup
  48. van den Hoogen LL, van der Linden M, Meyaard L, Fritsch-Stork RDE, van Roon JA, Radstake TR. Neutrophil Extracellular Traps and Low-Density Granulocytes Are Associated With the Interferon Signature in Systemic Lupus Erythematosus, But Not in Antiphospholipid Syndrome. Ann Rheumatic Dis 2020 79(10):e135–5.
    doi: 10.1136/annrheumdis-2019-215781pubmed: 31177097google scholar: lookup
  49. Keir HR, Chalmers JD. Neutrophil Extracellular Traps in Chronic Lung Disease: Implications for Pathogenesis and Therapy. Eur Respir Rev 2022 31(163).
    doi: 10.1183/16000617.0241-2021pmc: PMC9488971pubmed: 35197267google scholar: lookup
  50. Toussaint M, Jackson DJ, Swieboda D, Guedán A, Tsourouktsoglou TD, Ching YM. Host DNA Released by NETosis Promotes Rhinovirus-Induced Type-2 Allergic Asthma Exacerbation. Nat Med 2017 23(6):681–91.
    doi: 10.1038/nm.4332pmc: PMC5821220pubmed: 28459437google scholar: lookup
  51. Zou Y, Chen X, Xiao J, Bo Zhou D, Xiao Lu X, Li W. Neutrophil Extracellular Traps Promote Lipopolysaccharide-Induced Airway Inflammation and Mucus Hypersecretion in Mice. Oncotarget 2018 9(17):13276–86.
    doi: 10.18632/oncotarget.24022pmc: PMC5862577pubmed: 29568356google scholar: lookup
  52. de Melo MGM, Mesquita EDD, Oliveira MM, da Silva-Monteiro C, Silveira AKA, Malaquias TS. Imbalance of NET and Alpha-1-Antitrypsin in Tuberculosis Patients Is Related With Hyper Inflammation and Severe Lung Tissue Damage. Front Immunol 2019 9:3147.
    doi: 10.3389/fimmu.2018.03147pmc: PMC6335334pubmed: 30687336google scholar: lookup
  53. Cheng O, Palaniyar N. NET Balancing: A Problem in Inflammatory Lung Diseases. Front Immunol 2013 4.
    doi: 10.3389/fimmu.2013.00001pmc: PMC3553399pubmed: 23355837google scholar: lookup
  54. Chen X, Li Y, Qin L, He R, Hu C. Neutrophil Extracellular Trapping Network Promotes the Pathogenesis of Neutrophil-Associated Asthma Through Macrophages. Immunol Investigations 2021 50(5):544–61.
    doi: 10.1080/08820139.2020.1778720pubmed: 32552227google scholar: lookup
  55. Lande R, Ganguly D, Facchinetti V, Frasca L, Conrad C, Gregorio J. Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA–Peptide Complexes in Systemic Lupus Erythematosus. Sci Trans Med 2011 3(73):73ra19–9.
    doi: 10.1126/scitranslmed.3001180pmc: PMC3399524pubmed: 21389263google scholar: lookup
  56. Sangaletti S, Tripodo C, Chiodoni C, Guarnotta C, Cappetti B, Casalini P. Neutrophil Extracellular Traps Mediate Transfer of Cytoplasmic Neutrophil Antigens to Myeloid Dendritic Cells Toward ANCA Induction and Associated Autoimmunity. Blood 2012 120(15):3007–18.
    doi: 10.1182/blood-2012-03-416156pubmed: 22932797google scholar: lookup
  57. Wilson AS, Randall KL, Pettitt JA, Ellyard JI, Blumenthal A, Enders A. Neutrophil Extracellular Traps and Their Histones Promote Th17 Cell Differentiation Directly via TLR2. Nat Commun 2022 13(1):528.
    doi: 10.1038/s41467-022-28172-4pmc: PMC8792063pubmed: 35082281google scholar: lookup
  58. Krishnamoorthy N, Douda DN, Brüggemann TR, Ricklefs I, Duvall MG, Abdulnour REE. Neutrophil Cytoplasts Induce TH17 Differentiation and Skew Inflammation Toward Neutrophilia in Severe Asthma. Sci Immunol 2018 3(26):eaao4747.
    doi: 10.1126/sciimmunol.aao4747pmc: PMC6320225pubmed: 30076281google scholar: lookup
  59. Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory Airway Disease of Horses—Revised Consensus Statement. J Veterinary Internal Med 2016 30(2):503–15.
    doi: 10.1111/jvim.13824pmc: PMC4913592pubmed: 26806374google scholar: lookup
  60. Lavoie JP, Bullone M, Rodrigues N, Germim P, Albrecht B, von Salis-Soglio M. Effect of Different Doses of Inhaled Ciclesonide on Lung Function, Clinical Signs Related to Airflow Limitation and Serum Cortisol Levels in Horses With Experimentally Induced Mild to Severe Airway Obstruction. Equine Veterinary J 2019 51(6):779–86.
    doi: 10.1111/evj.13093pmc: PMC7379559pubmed: 30854685google scholar: lookup
  61. Gerber V, Straub R, Marti E, Hauptman J, Herholz C, King M. Endoscopic Scoring of Mucus Quantity and Quality: Observer and Horse Variance and Relationship to Inflammation, Mucus Viscoelasticity and Volume. Equine Vet J 2004 36(7):576–82.
    doi: 10.2746/0425164044864525pubmed: 15581321google scholar: lookup
  62. Hermange T, Le Corre S, Bizon C, Richard EA, Couroucé A. Bronchoalveolar Lavage Fluid From Both Lungs in Horses: Diagnostic Reliability of Cytology From Pooled Samples. Veterinary J 2019 244:28–33.
    doi: 10.1016/j.tvjl.2018.12.002pubmed: 30825891google scholar: lookup
  63. Kano H, Huq M, Tsuda M, Noguchi H, Takeyama N. Sandwich ELISA for Circulating Myeloperoxidase- and Neutrophil Elastase-DNA Complexes Released From Neutrophil Extracellular Traps. Adv Techniques Biol Med 2017 05.
    doi: 10.4172/2379-1764.1000196google scholar: lookup
  64. Rebordão MR, Carneiro C, Alexandre-Pires G, Brito P, Pereira C, Nunes T. Neutrophil Extracellular Traps Formation by Bacteria Causing Endometritis in the Mare. J Reprod Immunol 2014 106:41–9.
    doi: 10.1016/j.jri.2014.08.003pubmed: 25218891google scholar: lookup
  65. Uddin M, Watz H, Malmgren A, Pedersen F. NETopathic Inflammation in Chronic Obstructive Pulmonary Disease and Severe Asthma. Front Immunol 2019 10.
    doi: 10.3389/fimmu.2019.00047pmc: PMC6370641pubmed: 30804927google scholar: lookup
  66. Lachowicz-Scroggins ME, Dunican EM, Charbit AR, Raymond W, Looney MR, Peters MC. Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma. Am J Respir Crit Care Med 2019 199(9):1076–85.
    doi: 10.1164/rccm.201810-1869OCpmc: PMC6515873pubmed: 30888839google scholar: lookup
  67. Radermecker C, Louis R, Bureau F, Marichal T. Role of Neutrophils in Allergic Asthma. Curr Opin Immunol 2018 54:28–34.
    doi: 10.1016/j.coi.2018.05.006pubmed: 29883877google scholar: lookup
  68. Wright TK, Gibson PG, Simpson JL, McDonald VM, Wood LG, Baines KJ. Neutrophil Extracellular Traps Are Associated With Inflammation in Chronic Airway Disease. Respirology 2016 21(3):467–75.
    doi: 10.1111/resp.12730pubmed: 26804470google scholar: lookup
  69. Beekman L, Tohver T, Léguillette R. Comparison of Cytokine mRNA Expression in the Bronchoalveolar Lavage Fluid of Horses With Inflammatory Airway Disease and Bronchoalveolar Lavage Mastocytosis or Neutrophilia Using REST Software Analysis. J Veterinary Internal Med 2012 26(1):153–61.
    doi: 10.1111/j.1939-1676.2011.00847.xpubmed: 22168153google scholar: lookup
  70. Pirie RS. Mild to Moderate Equine Asthma — An Overview. Livestock 2017 22(3):158–63.
    doi: 10.12968/live.2017.22.3.158google scholar: lookup
  71. Thålin C, Daleskog M, Göransson SP, Schatzberg D, Lasselin J, Laska AC. Validation of an Enzyme-Linked Immunosorbent Assay for the Quantification of Citrullinated Histone H3 as a Marker for Neutrophil Extracellular Traps in Human Plasma. Immunol Res 2017 65(3):706–12.
    doi: 10.1007/s12026-017-8905-3pmc: PMC5440486pubmed: 28161762google scholar: lookup
  72. Guiducci E, Lemberg C, Küng N, Schraner E, Theocharides APA, LeibundGut-Landmann S. Candida Albicans-Induced NETosis Is Independent of Peptidylarginine Deiminase 4. Front Immunol 2018 9.
    doi: 10.3389/fimmu.2018.01573pmc: PMC6046457pubmed: 30038623google scholar: lookup
  73. Franck T, Grulke S, Deby-Dupont G, Deby C, Duvivier H, Peters F. Development of an Enzyme-Linked Immunosorbent Assay for Specific Equine Neutrophil Myeloperoxidase Measurement in Blood. J Vet Diagn Invest 2005 17(5):412–9.
    doi: 10.1177/104063870501700502pubmed: 16312231google scholar: lookup
  74. Mathy-Hartert M, Bourgeois E, Grülke S, Deby-Dupont G, Caudron I, Deby C. Purification of Myeloperoxidase From Equine Polymorphonuclear Leucocytes. Can J Vet Res 1998 62(2):127–32.
    pmc: PMC1189459pubmed: 9553712
  75. Bullone M, de Lagarde M, Vargas A, Lavoie JP. Serum Surfactant Protein D and Haptoglobin as Potential Biomarkers for Inflammatory Airway Disease in Horses. J Veterinary Internal Med 2015 29(6):1707–11.
    doi: 10.1111/jvim.13602pmc: PMC4895656pubmed: 26289543google scholar: lookup
  76. Gy C, Leclere M, Vargas A, Grimes C, Lavoie JP. Investigation of Blood Biomarkers for the Diagnosis of Mild to Moderate Asthma in Horses. J Veterinary Internal Med 2019 33(4):1789–95.
    doi: 10.1111/jvim.15505pmc: PMC6639487pubmed: 31099114google scholar: lookup
  77. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Acute Phase Proteins in Racehorses With Inflammatory Airway Disease. J Vet Intern Med 2015 29(3):940–5.
    doi: 10.1111/jvim.12587pmc: PMC4895423pubmed: 25857218google scholar: lookup
  78. Niedźwiedź A, Jaworski Z, Kubiak K. Circulating Immune Complexes and Markers of Systemic Inflammation in RAO-Affected Horses. Pol J Vet Sci 2014 17(4):697–702.
    doi: 10.2478/pjvs-2014-0101pubmed: 25638984google scholar: lookup
  79. Barton AK, Shety T, Bondzio A, Einspanier R, Gehlen H. Metalloproteinases and Their Tissue Inhibitors in Comparison Between Different Chronic Pneumopathies in the Horse. Mediators Inflamm 2015 2015:569512.
    doi: 10.1155/2015/569512pmc: PMC4681803pubmed: 26770019google scholar: lookup
  80. du Preez S, Raidal SL, Doran GS, Prescott M, Hughes KJ. Exhaled Breath Condensate Hydrogen Peroxide, pH and Leukotriene B4 Are Associated With Lower Airway Inflammation and Airway Cytology in the Horse. Equine Vet J 2019 51(1):24–32.
    doi: 10.1111/evj.12979pubmed: 29917256google scholar: lookup
  81. Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Apostolidou E, Kourtzelis I. Neutrophil Extracellular Trap Formation Is Associated With IL-1β and Autophagy-Related Signaling in Gout. PLoS One 2011 6(12):e29318.
    doi: 10.1371/journal.pone.0029318pmc: PMC3241704pubmed: 22195044google scholar: lookup
  82. Meher AK, Spinosa M, Davis JP, Pope N, Laubach VE, Su G. Novel Role of IL (Interleukin)-1β in Neutrophil Extracellular Trap Formation and Abdominal Aortic Aneurysms. Arteriosclerosis Thrombosis Vasc Biol 2018 38(4):843–53.
    doi: 10.1161/ATVBAHA.117.309897pmc: PMC5864548pubmed: 29472233google scholar: lookup
  83. Ainsworth DM, Matychak M, Reyner CL, Erb HN, Young JC. Effects of In Vitro Exposure to Hay Dust on the Gene Expression of Chemokines and Cell-Surface Receptors in Primary Bronchial Epithelial Cell Cultures Established From Horses With Chronic Recurrent Airway Obstruction. Am J Vet Res 2009 70(3):365–72.
    doi: 10.2460/ajvr.70.3.365pubmed: 19254149google scholar: lookup
  84. Teijeira Á, Garasa S, Gato M, Alfaro C, Migueliz I, Cirella A. CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps That Interfere With Immune Cytotoxicity. Immunity 2020 52(5):856–71.e8.
    doi: 10.1016/j.immuni.2020.03.001pubmed: 32289253google scholar: lookup
  85. Dworski R, Simon HU, Hoskins A, Yousefi S. Eosinophil and Neutrophil Extracellular DNA Traps in Human Allergic Asthmatic Airways. J Allergy Clin Immunol 2011 127(5):1260–6.
    doi: 10.1016/j.jaci.2010.12.1103pmc: PMC3085562pubmed: 21315435google scholar: lookup
  86. Clancy DM, Henry CM, Sullivan GP, Martin SJ. Neutrophil Extracellular Traps can Serve as Platforms for Processing and Activation of IL-1 Family Cytokines. FEBS J 2017 284(11):1712–25.
    doi: 10.1111/febs.14075pubmed: 28374518google scholar: lookup
  87. Conforti A, Wahlers T, Paunel-Görgülü A. Neutrophil Extracellular Traps Modulate Inflammatory Markers and Uptake of Oxidized LDL by Human and Murine Macrophages. PLoS One 2021 16(11):e0259894.
    doi: 10.1371/journal.pone.0259894pmc: PMC8604363pubmed: 34797846google scholar: lookup
  88. Prikk K, Maisi P, Pirilä E, Reintam MA, Salo T, Sorsa T. Airway Obstruction Correlates With Collagenase-2 (MMP-8) Expression and Activation in Bronchial Asthma. Lab Invest 2002 82(11):1535–45.
    doi: 10.1097/01.LAB.0000035023.53893.B6pubmed: 12429813google scholar: lookup
  89. Prikk K, Pirilä E, Sepper R, Maisi P, Salo T, Wahlgren J. In Vivo Collagenase-2 (MMP-8) Expression by Human Bronchial Epithelial Cells and Monocytes/Macrophages in Bronchiectasis. J Pathol 2001 194(2):232–8.
    doi: 10.1002/path.849pubmed: 11400153google scholar: lookup
  90. Porto BN, Stein RT. Neutrophil Extracellular Traps in Pulmonary Diseases: Too Much of a Good Thing?. Front Immunol 2016 7.
    doi: 10.3389/fimmu.2016.00311pmc: PMC4983612pubmed: 27574522google scholar: lookup
  91. Linssen RS, Chai G, Ma J, Kummarapurugu AB, van Woensel JBM, Bem RA. Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit. Am J Respir Cell Mol Biol 2021 64(1):69–78.
    doi: 10.1165/rcmb.2020-0168OCpmc: PMC7780998pubmed: 33095650google scholar: lookup
  92. Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S. Gene Set Enrichment Analysis of the Bronchial Epithelium Implicates Contribution of Cell Cycle and Tissue Repair Processes in Equine Asthma. Sci Rep 2018 8(1):16408.
    doi: 10.1038/s41598-018-34636-9pmc: PMC6219531pubmed: 30401798google scholar: lookup
  93. Lavoie JP, Cesarini C, Lavoie-Lamoureux A, Moran K, Lutz S, Picandet V. Bronchoalveolar Lavage Fluid Cytology and Cytokine Messenger Ribonucleic Acid Expression of Racehorses With Exercise Intolerance and Lower Airway Inflammation. J Veterinary Internal Med 2011 25(2):322–9.
    doi: 10.1111/j.1939-1676.2010.0664.xpubmed: 21281348google scholar: lookup

Citations

This article has been cited 15 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. Salinas-Varas C, Espinosa G, Muñoz-Caro T, Conejeros I, Gärtner U, Fey K, Arnhold S, Taubert A, Hermosilla C. Equine adipose-derived stem cells modulate in vitro neutrophil extracellular trap release by polymorphonuclear neutrophils. Front Vet Sci 2025;12:1685757.
    doi: 10.3389/fvets.2025.1685757pubmed: 41200546google 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. Tonello S, Vercellino N, D'Onghia D, Fracchia A, Caria G, Sola D, Tillio PA, Sainaghi PP, Colangelo D. Extracellular Traps in Inflammation: Pathways and Therapeutic Targets. Life (Basel) 2025 Apr 8;15(4).
    doi: 10.3390/life15040627pubmed: 40283181google scholar: lookup
  5. 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
  6. Peng B, Yan MY, Chen YR, Sun F, Xiang XD, Liu D. The methyl-CpG binding domain 2 regulates peptidylarginine deiminase 4 expression and promotes neutrophil extracellular trap formation via the Janus kinase 2 signaling pathway in experimental severe asthma. Ann Med 2025 Dec;57(1):2458207.
    doi: 10.1080/07853890.2025.2458207pubmed: 39865866google scholar: lookup
  7. Lendl L, Barton AK. Equine Asthma Diagnostics: Review of Influencing Factors and Difficulties in Diagnosing Subclinical Disease. Animals (Basel) 2024 Dec 4;14(23).
    doi: 10.3390/ani14233504pubmed: 39682469google scholar: lookup
  8. Long D, Mao C, Xu Y, Zhu Y. The emerging role of neutrophil extracellular traps in ulcerative colitis. Front Immunol 2024;15:1425251.
    doi: 10.3389/fimmu.2024.1425251pubmed: 39170617google scholar: lookup
  9. Gao G, Hao YQ, Wang C, Gao P. Role and regulators of N(6)-methyladenosine (m(6)A) RNA methylation in inflammatory subtypes of asthma: a comprehensive review. Front Pharmacol 2024;15:1360607.
    doi: 10.3389/fphar.2024.1360607pubmed: 39108751google scholar: lookup
  10. Xue GZ, Ma HZ, Wuren TN. The role of neutrophils in chronic cough. Hum Cell 2024 Sep;37(5):1316-1324.
    doi: 10.1007/s13577-024-01089-4pubmed: 38913146google scholar: lookup
  11. Simões J, Tilley P. Decision Making in Severe Equine Asthma-Diagnosis and Monitoring. Animals (Basel) 2023 Dec 16;13(24).
    doi: 10.3390/ani13243872pubmed: 38136909google scholar: lookup
  12. 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
  13. Henneck T, Krüger C, Nerlich A, Langer M, Fingerhut L, Bonilla MC, Meurer M, von den Berg S, de Buhr N, Branitzki-Heinemann K, von Köckritz-Blickwede M. Comparison of NET quantification methods based on immunofluorescence microscopy: Hand-counting, semi-automated and automated evaluations. Heliyon 2023 Jun;9(6):e16982.
    doi: 10.1016/j.heliyon.2023.e16982pubmed: 37484269google scholar: lookup
  14. Salinas C, Barriga K, Albornoz A, Alarcon P, Quiroga J, Uberti B, Sarmiento J, Henriquez C, Ehrenfeld P, Burgos RA, Moran G. Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses. Front Vet Sci 2022;9:1025249.
    doi: 10.3389/fvets.2022.1025249pubmed: 36686170google scholar: lookup
  15. Sokolov AV, Chernyak BV, Zinovkin RA, Hwang TL, Sud'ina GF. Editorial: Pharmacological approaches targeting neutrophilic inflammation: Volume II. Front Pharmacol 2022;13:1084026.
    doi: 10.3389/fphar.2022.1084026pubmed: 36483745google scholar: lookup
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