Neutrophils’ Extracellular Trap Mechanisms: From Physiology to Pathology

Abstract

Neutrophils are an essential part of the innate immune system and the first line of defense against invading pathogens. They phagocytose, release granular contents, produce reactive oxygen species, and form neutrophil extracellular traps (NETs) to fight pathogens. With the characterization of NETs and their components, neutrophils were identified as players of the innate adaptive crosstalk. This has placed NETs at the center not only of physiological but also pathological processes. Aside from their role in pathogen uptake and clearance, NETs have been demonstrated to contribute to the resolution of inflammation by forming aggregated NETs able to degrade inflammatory mediators. On the other hand, NETs have the potential to foster severe pathological conditions. When homeostasis is disrupted, they occlude vessels and ducts, serve as sources of autoantigens and danger or damage associated molecular patterns, directly damage tissues, and exaggerate complement activity and inflammation. This review focusses on the understanding of NETs from their formation to their functions in both physiological and pathological processes.

Macrophages Coordinate Immune Response to Laser-Induced Injury via Extracellular Traps

“…Among the significantly upregulated transcripts, we observed cytochrome b ( Cyba and Cybb ), Rac family small GTPase 2 ( Rac2 ), integrin subunit beta 2 ( Itgb2 ), and neutrophil cytosolic factor 2 ( Ncf2 ). These genes have previously been shown to directly regulate neutrophil extracellular traps (NET) formation (10, 36–39). We also detected an upregulation of Casp4 and Vwf , both of which are involved in NET formation, facilitating nuclear expansion, lysis, and NET release (10, 40).…”

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“…Neutrophils were initially considered the first responders of the innate immune system against extracellular pathogens (Lehrer et al, 1988;Schoen et al, 2022). However, current evidence suggests that neutrophils are not only involved in the regulation of the innate and adaptive immune systems but can polarize toward different phenotypes in response to environmental signals (Hedrick and Malanchi, 2022).…”

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“…When the scaffold was implanted, neutrophils migrated around the scaffold within 24 h and prepared to recruit immune cells by secreting cytokines and releasing neutrophil extracellular traps (NETs). When neutrophils adhere to the surface of the scaffold (extracellular matrix), they are activated to excrete DNA and form neutrophil extracellular traps (NETs) (Schoen et al, 2022;Won FIGURE 4 Schematic of interactions of various signaling pathways under mechanical stimulation. Integrins, Wnt receptors, and Ca2+ channels were stimulated by mechanical stimulation, thereby inducing a series of transcription factors to regulate osteoblast proliferation and differentiation.…”

“…When the scaffold was implanted, neutrophils migrated around the scaffold within 24 h and prepared to recruit immune cells by secreting cytokines and releasing neutrophil extracellular traps (NETs). When neutrophils adhere to the surface of the scaffold (extracellular matrix), they are activated to excrete DNA and form neutrophil extracellular traps (NETs) ( Schoen et al, 2022 ; Won et al, 2020 ) fabricated hierarchically structured “microchannel” 3D printed scaffolds by the 3D printing of a polycaprolactone polymer. Compared to non-microchannel scaffolds made of the same material, the neutrophil-capturing net can be reduced, which is beneficial for tissue repair.…”