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Review
. 2017 Jan 11:7:678.
doi: 10.3389/fimmu.2016.00678. eCollection 2016.

NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils

Alexandros Mitsios  1 , Athanasios Arampatzioglou  1 , Stella Arelaki  2 , Ioannis Mitroulis  3 , Konstantinos Ritis  4
Affiliations
Review

NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils

Alexandros Mitsios et al. Front Immunol. .

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.

Keywords: autoimmunity; autoinflammation; neutrophil; neutrophil extracellular traps; thromboinflammation.

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Figures

Figure 1
Figure 1
Neutrophil extracellular trap (NET) formation and protein decoration. Representative images taken using confocal microscopy, demonstrating (A) NET formation mechanism and (B,C) the two-step process through which the disease-related protein is externalized.
Figure 2
Figure 2
NETopathies are ruled by the bioactive disease-related neutrophil extracellular trap (NET) proteins. The clinical manifestations of (A) thrombosis, (B) systemic lupus erythematosus, (C) rheumatoid athritis (RA), (D) pulmonary fibrosis and psoriasis, (E) familiar Mediterranean fever are determined by the NET-mediated exposure of bioactive disease-related proteins.
Figure 3
Figure 3
Targeting neutrophil extracellular trap (NET) formation or integrity, or specific NET proteins, promises novel therapeutic strategies. (A) Hydroxychloroquine inhibits NET formation through its anti-autophagic activity. (B) rhDNase and DNase I dismantle NET structures. (C) Anti-interleukin 17 (IL-17) and anti-interleukin 1 beta (IL-1β) antibodies blockade bioactive IL-17 and IL-1β on NETs, respectively.
See this image and copyright information in PMC

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