Ripening and Degradation Mechanisms of Neutrophil Extracellular Traps

Dear Colleagues,

Neutrophil Extracellular Traps (NETs) represent a crucial element of the innate immune response, formed by the release of decondensed chromatin fibers and associated proteins from neutrophils. These structures play a vital role in capturing and neutralizing pathogens. However, the formation and degradation of NETs are tightly regulated processes, and any imbalance can lead to pathological conditions, including chronic inflammation, autoimmune diseases, and thrombosis.

NET formation, or NETosis, can occur through suicidal or vital pathways, each involving distinct cellular mechanisms. Suicidal NETosis typically requires chromatin decondensation mediated by enzymes such as peptidyl arginine deiminase 4 (PAD4) and neutrophil elastase (NE), followed by rupture of the nuclear and plasma membranes. Vital NETosis, on the other hand, can occur without neutrophil death, involving mechanisms like nuclear blebbing or mitochondrial DNA release.

Aggregated NETs (aggNETs) play a significant role in resolving inflammation by sequestering and degrading inflammatory mediators. However, these structures can also contribute to pathological conditions if not properly cleared.

The impaired degradation or excessive formation of NETs can lead to their persistence in tissues, contributing to the development of various diseases. For example, in autoimmune conditions like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), NET remnants can act as sources of autoantigens, promoting the formation of autoantibodies and immune complexes. Similarly, in thrombotic diseases, NETs can promote coagulation and thrombosis, exacerbating vascular damage. Many more diseases are influenced by the impaired degradation of NETs.

The processes of NET degradation are not fully understood but are primarily mediated by DNases, such as DNase1 and DNase1L3, which break down the DNA backbone of NETs. This process is crucial for preventing prolonged inflammation and autoimmunity. Macrophages and dendritic cells also participate in the clearance of NETs through processes like micropinocytosis and extracellular digestion.

This Special Issue seeks original papers and reviews on the mechanisms of the extracellular modification and degradation of NETs and their impact on health and disease.

Prof. Dr. Martin Herrmann
Dr. Maximilian Dölling
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• neutrophil extracellular traps
• degradation of NETs
• ripening of NETs