The Pathophysiological Role of Neutrophil Extracellular Traps in Inflammatory Diseases

Abstract

Neutrophil pathogen-killing mechanism termed neutrophil extracellular traps (NETs) has been recently identified. NETs consist of chromatin and histones along with serine proteases and myeloperoxidase and are induced by a great variety of infectious and non-infectious stimuli. NETosis is a kind of programmed neutrophil death characterized by chromatin decondensation and release of nuclear granular contents, mainly driven by peptidylarginine deiminase 4 citrullination of histones. Although classically related to the protection against infectious pathogens, nowadays NETs have been described as a player of several pathophysiological processes. Neutrophil dysregulation has been demonstrated in the pathogenesis of most representative vascular diseases, such as acute coronary syndrome, stroke and venous thrombosis. Indeed, NETs have been identified within atherosclerotic lesions and arterial thrombi in both human beings and animal models. Moreover, an imbalance in this mechanism has been proposed as a critical source of modified and/or externalized autoantigens in autoimmune and inflammatory diseases. Finally, an update on the role of NETs in the pathogenesis of cancer has been included. In the present review, based on papers released on PubMed and MEDLINE up to July 2017, we point to update the knowledge on NETs, from their structure to their roles in infectious diseases as well as in cardiovascular diseases, autoimmunity, metabolic disorders and cancer, with a look to future perspectives and therapeutic opportunities.

Oxidant sensor cation channel TRPM2 regulates neutrophil extracellular trap formation and protects against pneumoseptic bacterial infection

“…These findings provide evidence for a novel role of TRPM2 in regulating NET formation with an important protective role in pneumoseptic bacterial infection owing to the antimicrobial activity of NETs. Although speculative at this point, reduced inflammation and improved disease outcome reported in absence of TRPM2 in sterile inflammatory diseases may be the result of impaired NET formation because exuberant NET formation is associated with exacerbation of inflammation in autoimmune diseases (8,55,56). Our studies thus open up a new avenue to research in this area and introduce the potential of TRPM2 modulation as a promising immunomodulatory strategy for NET-associated pathologies.…”

Pharmacological effects of the isomeric mixture of alpha and beta amyrin from Protium heptaphyllum: a literature review

“…The natural pentacyclic triterpenoid, ursolic acid, has been known to possess potent anti-inflammatory, antioxidant, and antinociceptive effects in various animal models [19]. In several studies, AMY has also demonstrated a great pharmacological applicability in several diseases [17][18][19][20][21] that have a common feature in their development: inflammation as one of the main mechanisms involved in their genesis [22,23]. AMY demonstrated peripheral and central analgesic effects independent of the opioid system and also showed a potent anti-inflammatory activity.…”

Neutrophil Extracellular Traps and Cardiovascular Diseases: An Update

“…More recently, neutrophil extracellular traps (NETs) have been recognized as an additional mechanism of defense through a process called NETosis [4,5]. NETs are made up of chromatin decorated with histones, proteases, and granular proteins through which neutrophils can block and catch up invading microorganisms [6,7] (Figure 1). The presence of granular proteins is an essential requirement for NET formation since both NE knockout mice and MPO-deficient patients were found to produce a Figure 1.…”