Neutrophil Extracellular Trap (NET) Formation: Mechanism, Disease and Drugs

Dear Colleagues,

Extensive research work conducted over the last decade shows that neutrophils and certain other immune cells release chromatin and mitochondrial DNA coated with antimicrobial peptides and proteases as extracellular traps (NETs). NET formation is a complex process involving multiple steps, including NADPH oxidase-mediated and mitochondrial ROS production, glycolytic ATP production, activation of the cytoskeleton, kinase cascades, granular proteins coating DNA, and increases in intracellular calcium. Several studies suggest that different types of cell death could lead to NET formation (NETosis, autophagic cell death, necroptosis).

Different agonists, cell–cell interactions, external millilux, and intercellular changes regulate NET formations in various infectious, inflammatory, and autoimmune diseases. The involvement of NETs in several other diseases including cancer and cardiovascular conditions has also been reported. Relative contributions of NETs to microbial killing, compared to other tissue-specific microbicidal innate immune proteins and pathways such as complement activation, are also not fully explored. Although NETs have been considered an important antimicrobial component, it is now apparent that NETs are detrimental when formed out of context, especially during chronic inflammatory conditions.

Once NETs are released, they may be degraded by nucleases and cleared by phagocytes including macrophages. Breaking NETs with DNase I is reported to reduce tissue damage. However, suppressing excess NET formation is now considered a useful option to limit the negative effects of NETs while maintaining the phagocytic functions of neutrophils. Drugs that would regulate NET formation may hold therapeutic potential for treating NET-related diseases.

For this Special Issue, we encourage the submission of articles that describe novel mechanistic insights, NET formation agonists and antagonists, and potential drugs, for various NET-related diseases and conditions.

Dr. Nades Palaniyar
Dr. Hans-Uwe Simon
Dr. Victor Nizet
Guest Editors

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