Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.
Extracellular Traps/physiology* ; Humans ; Atherosclerosis/immunology* ; Neutrophils/physiology* ; Leukocyte Elastase/metabolism* ; Peroxidase/physiology* ; Matrix Metalloproteinases/physiology* ; Cathepsin G/metabolism* ; Cathelicidins ; HMGB1 Protein/physiology* ; Histones ; Animals ; Endothelium, Vascular

Neutrophil extracellular traps (NETs) represent a form of cell death distinct from apoptosis or necrosis. The imbalance between the formation and degradation of NETs has long been considered to be closely associated with the activity of autoimmune diseases such as systemic lupus erythematous (SLE). Reactive oxygen species derived from the nicotinamide adenine dinucleotide phosphate oxidase pathway or mitochondrial DNA pathway play a key role in the primary stage of NETs formation. The exposure or delayed degradation of abundant autoantigens, such as double-strand DNA, caused by abnormal activation of neutrophils can induce autoantibody to form immune complexes that deposit in local tissues and then induce the plasmacytoid dendritic cells to secrete the interferon alpha and other inflammatory factors. Those inflammatory factors will eventually cause endothelial cell injury. In order to provide a theoretical basis for targeted therapy and diagnosis of childhood-onset SLE, this paper reviews the role of NETs in the pathogenesis of SLE.
Extracellular Traps ; Humans ; Lupus Erythematosus, Systemic ; etiology ; therapy ; Neutrophils ; physiology

OBJECTIVEAsthma and chronic obstructive pulmonary disease (COPD) are representative chronic inflammatory airway diseases responsible for a considerable burden of disease. In this article, we reviewed the relationship between neutrophil extracellular traps (NETs) and chronic inflammatory airway diseases.

DATA SOURCESArticles published up to January 1, 2017, were selected from the PubMed, Ovid Medline, Embase databases, with the keywords of "asthma" or "pulmonary disease, chronic obstructive", "neutrophils" and "extracellular traps."

STUDY SELECTIONArticles were obtained and reviewed to analyze the role of NETs in asthma and COPD.

RESULTSNETs are composed of extracellular DNA, histones, and granular proteins, which are released from activated neutrophils. Multiple studies have indicated that there are a large amount of NETs in the airways of asthmatics and COPD patients. NETs can engulf and kill invading pathogens in the host. However, disordered regulation of NET formation has shown to be involved in the development of asthma and COPD. An overabundance of NETs in the airways or lung tissue could cause varying degrees of damage to lung tissues by inducing the death of human epithelial and endothelial cells, and thus resulting in impairing pulmonary function and accelerating the progress of the disease.

CONCLUSIONSExcessive NETs accumulate in the airways of asthmatics and COPD patients. Although NETs play an essential role in the innate immune system against infection, excessive components of NETs can cause lung tissue damage and accelerate disease progression in asthmatics and COPD patients. These findings suggest that administration of NETs could be a novel approach to treat asthma and COPD. Mechanism studies, clinical practice, and strategies to regulate neutrophil activation or directly interrupt NET function in asthmatics and COPD patients are desperately needed.

Animals ; Asthma ; metabolism ; pathology ; Extracellular Traps ; metabolism ; physiology ; Humans ; Neutrophils ; metabolism ; pathology ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology