NETopathies? Unraveling the Dark Side of Old Diseases Through Neutrophils

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2017 Jan 27

PMID 28123386

Citations 33

Authors

Alexandros Mitsios

Athanasios Arampatzioglou

Stella Arelaki

Ioannis Mitroulis

Konstantinos Ritis

Affiliations

Soon will be listed here.

Abstract

Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance.

Citing Articles

"The NET effect": Neutrophil extracellular traps-a potential key component of the dysregulated host immune response in sepsis.

Retter A, Singer M, Annane D Crit Care. 2025; 29(1):59.

PMID: 39905519 PMC: 11796136. DOI: 10.1186/s13054-025-05283-0.

Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn's disease through IFNα pathway.

Gavriilidis E, Divolis G, Natsi A, Kafalis N, Kogias D, Antoniadou C Front Immunol. 2024; 15:1447608.

PMID: 39346917 PMC: 11427415. DOI: 10.3389/fimmu.2024.1447608.

Neutrophil extracellular traps in CSF and serum of dogs with steroid-responsive meningitis-arteritis.

Wohlsein J, Meurer M, Morgelin M, Nessler J, Flegel T, Schenk H PLoS One. 2024; 19(1):e0295268.

PMID: 38241272 PMC: 10798544. DOI: 10.1371/journal.pone.0295268.

Effect of Antioxidant Supplementation on NET Formation Induced by LPS In Vitro; the Roles of Vitamins E and C, Glutathione, and N-acetyl Cysteine.

Munoz-Sanchez G, Godinez-Mendez L, Fafutis-Morris M, Delgado-Rizo V Int J Mol Sci. 2023; 24(17).

PMID: 37685966 PMC: 10487622. DOI: 10.3390/ijms241713162.

Ιnterleukin-17A-Enriched Neutrophil Extracellular Traps Promote Immunofibrotic Aspects of Childhood Asthma Exacerbation.

Ntinopoulou M, Cassimos D, Roupakia E, Kolettas E, Panopoulou M, Mantadakis E Biomedicines. 2023; 11(8).

PMID: 37626601 PMC: 10452671. DOI: 10.3390/biomedicines11082104.

References

Caudrillier A, Kessenbrock K, Gilliss B, Nguyen J, Marques M, Monestier M . Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest. 2012; 122(7):2661-71. PMC: 3386815. DOI: 10.1172/JCI61303. View

van Montfoort M, Stephan F, Lauw M, Hutten B, van Mierlo G, Solati S . Circulating nucleosomes and neutrophil activation as risk factors for deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2012; 33(1):147-51. DOI: 10.1161/ATVBAHA.112.300498. View

Meng W, Paunel-Gorgulu A, Flohe S, Hoffmann A, Witte I, MacKenzie C . Depletion of neutrophil extracellular traps in vivo results in hypersusceptibility to polymicrobial sepsis in mice. Crit Care. 2012; 16(4):R137. PMC: 3580722. DOI: 10.1186/cc11442. View

Maueroder C, Kienhofer D, Hahn J, Schauer C, Manger B, Schett G . How neutrophil extracellular traps orchestrate the local immune response in gout. J Mol Med (Berl). 2015; 93(7):727-34. DOI: 10.1007/s00109-015-1295-x. View

Mishalian I, Bayuh R, Levy L, Zolotarov L, Michaeli J, Fridlender Z . Tumor-associated neutrophils (TAN) develop pro-tumorigenic properties during tumor progression. Cancer Immunol Immunother. 2013; 62(11):1745-56. PMC: 11028422. DOI: 10.1007/s00262-013-1476-9. View

Kahn S, Cooper M, Del Prato S . Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 2013; 383(9922):1068-83. PMC: 4226760. DOI: 10.1016/S0140-6736(13)62154-6. View

Cedervall J, Zhang Y, Huang H, Zhang L, Femel J, Dimberg A . Neutrophil Extracellular Traps Accumulate in Peripheral Blood Vessels and Compromise Organ Function in Tumor-Bearing Animals. Cancer Res. 2015; 75(13):2653-62. DOI: 10.1158/0008-5472.CAN-14-3299. View

Berger-Achituv S, Brinkmann V, Abu Abed U, Kuhn L, Ben-Ezra J, Elhasid R . A proposed role for neutrophil extracellular traps in cancer immunoediting. Front Immunol. 2013; 4:48. PMC: 3589747. DOI: 10.3389/fimmu.2013.00048. View

Yalavarthi S, Gould T, Rao A, Mazza L, Morris A, Nunez-Alvarez C . Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: a newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol. 2015; 67(11):2990-3003. PMC: 4626310. DOI: 10.1002/art.39247. View

10.

Chrysanthopoulou A, Mitroulis I, Apostolidou E, Arelaki S, Mikroulis D, Konstantinidis T . Neutrophil extracellular traps promote differentiation and function of fibroblasts. J Pathol. 2014; 233(3):294-307. DOI: 10.1002/path.4359. View

11.

Villanueva E, Yalavarthi S, Berthier C, Hodgin J, Khandpur R, Lin A . Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus. J Immunol. 2011; 187(1):538-52. PMC: 3119769. DOI: 10.4049/jimmunol.1100450. View

12.

Savchenko A, Martinod K, Seidman M, Wong S, Borissoff J, Piazza G . Neutrophil extracellular traps form predominantly during the organizing stage of human venous thromboembolism development. J Thromb Haemost. 2014; 12(6):860-70. PMC: 4055516. DOI: 10.1111/jth.12571. View

13.

Yeh T, Chang H, Liang C, Wu J, Liu M . Deoxyribonuclease-inhibitory antibodies in systemic lupus erythematosus. J Biomed Sci. 2003; 10(5):544-51. DOI: 10.1159/000072382. View

14.

Cools-Lartigue J, Spicer J, Najmeh S, Ferri L . Neutrophil extracellular traps in cancer progression. Cell Mol Life Sci. 2014; 71(21):4179-94. PMC: 7096049. DOI: 10.1007/s00018-014-1683-3. View

15.

Lewis H, Liddle J, Coote J, Atkinson S, Barker M, Bax B . Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015; 11(3):189-91. PMC: 4397581. DOI: 10.1038/nchembio.1735. View

16.

Tang S, Zhang Y, Yin S, Gao X, Shi W, Wang Y . Neutrophil extracellular trap formation is associated with autophagy-related signalling in ANCA-associated vasculitis. Clin Exp Immunol. 2015; 180(3):408-18. PMC: 4449769. DOI: 10.1111/cei.12589. View

17.

Knight J, Carmona-Rivera C, Kaplan M . Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases. Front Immunol. 2012; 3:380. PMC: 3521997. DOI: 10.3389/fimmu.2012.00380. View

18.

Spicer J, McDonald B, Cools-Lartigue J, Chow S, Giannias B, Kubes P . Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Res. 2012; 72(16):3919-27. DOI: 10.1158/0008-5472.CAN-11-2393. View

19.

Dubois A, Gauthier A, Brea D, Varaigne F, Diot P, Gauthier F . Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum. Am J Respir Cell Mol Biol. 2012; 47(1):80-6. DOI: 10.1165/rcmb.2011-0380OC. View

20.

Nakazawa D, Tomaru U, Yamamoto C, Jodo S, Ishizu A . Abundant neutrophil extracellular traps in thrombus of patient with microscopic polyangiitis. Front Immunol. 2012; 3:333. PMC: 3495275. DOI: 10.3389/fimmu.2012.00333. View