On Neutrophil Extracellular Trap (NET) Removal: What We Know Thus Far and Why So Little

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2020 Sep 16

PMID 32932841

Citations 18

Authors

Michal Santocki

Elzbieta Kolaczkowska

Affiliations

Soon will be listed here.

Abstract

Although neutrophil extracellular traps (NETs) were discovered only 16 years ago, they have already taken us from heaven to hell as we learned that apart from beneficial trapping of pathogens, they cause, or contribute to, numerous disorders. The latter is connected to their persistent presence in the blood or tissue, and we hardly know how they are removed in mild pathophysiological conditions and why their removal is impaired in multiple severe pathological conditions. Herein, we bring together all data available up till now on how NETs are cleared-from engaged cells, their phenotypes, to involved enzymes and molecules. Moreover, we hypothesize on why NET removal is challenged in multiple disorders and propose further directions for studies on NET removal as well as possible therapeutic strategies to have them cleared.

Citing Articles

Proteomic Profile Regulated by the Immunomodulatory Jusvinza Drug in Neutrophils Isolated from Rheumatoid Arthritis Patients.

Hernandez-Cedeno M, Rodriguez-Ulloa A, Ramos Y, Gonzalez L, Serrano-Diaz A, Zettl K Biomedicines. 2025; 12(12.

PMID: 39767648 PMC: 11727316. DOI: 10.3390/biomedicines12122740.

-induced NETs are highly cytotoxic on hepatic and colonic cells due to serine proteases and myeloperoxidase activities.

Jorge-Rosas F, Diaz-Godinez C, Garcia-Aguirre S, Martinez-Calvillo S, Carrero J Front Immunol. 2024; 15:1493946.

PMID: 39687618 PMC: 11646992. DOI: 10.3389/fimmu.2024.1493946.

The Application of Drugs and Nano-Therapies Targeting Immune Cells in Hypoxic Inflammation.

Luo J, Wang H, Chen J, Wei X, Feng J, Zhang Y Int J Nanomedicine. 2024; 19:3441-3459.

PMID: 38617798 PMC: 11015843. DOI: 10.2147/IJN.S456533.

Putative Role of Neutrophil Extracellular Trap Formation in Chronic Myeloproliferative Neoplasms.

Markovic D, Maslovaric I, Kovacic M, Vignjevic Petrinovic S, Ilic V Int J Mol Sci. 2023; 24(5).

PMID: 36901933 PMC: 10003516. DOI: 10.3390/ijms24054497.

DNase I and Sivelestat Ameliorate Experimental Hindlimb Ischemia-Reperfusion Injury by Eliminating Neutrophil Extracellular Traps.

Wang C, Wang Y, Jiang Q, Zeng Y, Yao Q, Liu X J Inflamm Res. 2023; 16:707-721.

PMID: 36852300 PMC: 9961174. DOI: 10.2147/JIR.S396049.

References

Skendros P, Mitsios A, Chrysanthopoulou A, Mastellos D, Metallidis S, Rafailidis P . Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis. J Clin Invest. 2020; 130(11):6151-6157. PMC: 7598040. DOI: 10.1172/JCI141374. View

Napirei M, Karsunky H, Zevnik B, Stephan H, Mannherz H, Moroy T . Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet. 2000; 25(2):177-81. DOI: 10.1038/76032. View

Urban C, Lourido S, Zychlinsky A . How do microbes evade neutrophil killing?. Cell Microbiol. 2006; 8(11):1687-96. DOI: 10.1111/j.1462-5822.2006.00792.x. View

Albrengues J, Shields M, Ng D, Park C, Ambrico A, Poindexter M . Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science. 2018; 361(6409). PMC: 6777850. DOI: 10.1126/science.aao4227. View

Cichon I, Ortmann W, Bednarz A, Lenartowicz M, Kolaczkowska E . Reduced Neutrophil Extracellular Trap (NET) Formation During Systemic Inflammation in Mice With Menkes Disease and Wilson Disease: Copper Requirement for NET Release. Front Immunol. 2020; 10:3021. PMC: 6974625. DOI: 10.3389/fimmu.2019.03021. View

Hermant B, Bibert S, Concord E, Dublet B, Weidenhaupt M, Vernet T . Identification of proteases involved in the proteolysis of vascular endothelium cadherin during neutrophil transmigration. J Biol Chem. 2003; 278(16):14002-12. DOI: 10.1074/jbc.M300351200. View

Parker H, Dragunow M, Hampton M, Kettle A, Winterbourn C . Requirements for NADPH oxidase and myeloperoxidase in neutrophil extracellular trap formation differ depending on the stimulus. J Leukoc Biol. 2012; 92(4):841-9. DOI: 10.1189/jlb.1211601. View

Thammavongsa V, Missiakas D, Schneewind O . Staphylococcus aureus degrades neutrophil extracellular traps to promote immune cell death. Science. 2013; 342(6160):863-6. PMC: 4026193. DOI: 10.1126/science.1242255. View

Homa J, Ortmann W, Kolaczkowska E . Conservative Mechanisms of Extracellular Trap Formation by Annelida Eisenia andrei: Serine Protease Activity Requirement. PLoS One. 2016; 11(7):e0159031. PMC: 4945018. DOI: 10.1371/journal.pone.0159031. View

10.

Shak S . Aerosolized recombinant human DNase I for the treatment of cystic fibrosis. Chest. 1995; 107(2 Suppl):65S-70S. DOI: 10.1378/chest.107.2_supplement.65s. View

11.

Gregoire M, Uhel F, Lesouhaitier M, Gacouin A, Guirriec M, Mourcin F . Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS. Eur Respir J. 2018; 52(2). DOI: 10.1183/13993003.02590-2017. View

12.

Li P, Li M, Lindberg M, Kennett M, Xiong N, Wang Y . PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010; 207(9):1853-62. PMC: 2931169. DOI: 10.1084/jem.20100239. View

13.

Okubo K, Kamiya M, Urano Y, Nishi H, Herter J, Mayadas T . Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation. EBioMedicine. 2016; 10:204-15. PMC: 5006695. DOI: 10.1016/j.ebiom.2016.07.012. View

14.

Manzenreiter R, Kienberger F, Marcos V, Schilcher K, Krautgartner W, Obermayer A . Ultrastructural characterization of cystic fibrosis sputum using atomic force and scanning electron microscopy. J Cyst Fibros. 2011; 11(2):84-92. DOI: 10.1016/j.jcf.2011.09.008. View

15.

Narasaraju T, Yang E, Perumal Samy R, Ng H, Poh W, Liew A . Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011; 179(1):199-210. PMC: 3123873. DOI: 10.1016/j.ajpath.2011.03.013. View

16.

Braian C, Hogea V, Stendahl O . Mycobacterium tuberculosis- induced neutrophil extracellular traps activate human macrophages. J Innate Immun. 2013; 5(6):591-602. PMC: 6741595. DOI: 10.1159/000348676. View

17.

Urban C, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W . Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog. 2009; 5(10):e1000639. PMC: 2763347. DOI: 10.1371/journal.ppat.1000639. View

18.

Keshari R, Jyoti A, Kumar S, Dubey M, Verma A, Srinag B . Neutrophil extracellular traps contain mitochondrial as well as nuclear DNA and exhibit inflammatory potential. Cytometry A. 2011; 81(3):238-47. DOI: 10.1002/cyto.a.21178. View

19.

Yu Y, Su K . Neutrophil Extracellular Traps and Systemic Lupus Erythematosus. J Clin Cell Immunol. 2013; 4. PMC: 3826916. DOI: 10.4172/2155-9899.1000139. View

20.

Napirei M, Ludwig S, Mezrhab J, Klockl T, Mannherz H . Murine serum nucleases--contrasting effects of plasmin and heparin on the activities of DNase1 and DNase1-like 3 (DNase1l3). FEBS J. 2009; 276(4):1059-73. DOI: 10.1111/j.1742-4658.2008.06849.x. View