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

Asthma is a chronic inflammatory disease of the airway involving various cellular players. Among the different phenotypes of asthma, neutrophilic asthma is often associated with severe airway inflammation and a notable resistance to corticosteroid treatment. Macrophages, as innate immune cells, play a crucial role in the pathogenesis of neutrophilic asthma. They regulate neutrophil recruitment and activation to promote the progression of airway inflammation. During this process, macrophages also undergo changes in aspects such as efferocytosis. We reviewed the recent research progresses regarding the role of macrophages in the pathogenesis of neutrophilic asthma, aiming to provide valuable insights for future studies in this area.
Humans ; Asthma/pathology* ; Neutrophils/pathology* ; Macrophages/immunology* ; Animals ; Phagocytosis

Lung cancer is one of the most common and lethal malignancies in China. In the context of the tumor microenvironment, neutrophil extracellular traps (NETs) released by neutrophils exert a profound impact on the occurrence and progression of lung cancer. Although the exact mechanisms by which NETs promote tumor growth have not been fully elucidated, existing research has revealed their multiple roles in tumor growth, invasion, metastasis, and cancer-related thrombosis. This article will review the molecular biology mechanisms and research progress of NETs in lung cancer based on recent studies.
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Extracellular Traps/metabolism* ; Humans ; Lung Neoplasms/drug therapy* ; Neutrophils/immunology* ; Animals ; Tumor Microenvironment

Neutrophil extracellular traps (NETs), intricate reticular structures released by activated neutrophils, play a pivotal regulatory role in the pathogenesis of malignant tumors. Lung cancer is one of the most prevalent malignancies globally, with persistently high incidence and mortality rates. Recent studies have revealed that NETs dynamically modulate the tumor microenvironment through unique pathological mechanisms, exhibiting complex immunoregulatory characteristics during the progression of lung cancer, and this discovery has increasingly become a focal point in tumor immunology research. This paper provides a comprehensive review of the latest advancements in NETs research related to lung cancer, offering an in-depth analysis of their impact on lung cancer progression, their potential diagnostic value, and the current state of research on targeting NETs for lung cancer prevention and treatment. The aim is to propose novel strategies to enhance therapeutic outcomes and improve the prognosis for lung cancer patients.
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Extracellular Traps/immunology* ; Humans ; Lung Neoplasms/metabolism* ; Neutrophils/metabolism* ; Animals ; Tumor Microenvironment

The pathogenesis of chronic sinusitis is complex, involving a variety of inflammatory cells and inflammatory mediators, and neutrophils play a key role in the pathological process of chronic sinusitis. Understanding the molecular basis of the pathogenesis of CRS is helpful for the precise diagnosis and treatment of chronic sinusitis. This article will systematically review the mechanism of neutrophils in the inflammatory response of the body, their role in the pathogenesis and treatment progress in CRS, and look forward to future research directions.
Humans ; Neutrophils ; Sinusitis/immunology* ; Chronic Disease

OBJECTIVES: To identify immunosuppressive neutrophil subsets in patients with prostate cancer (PCa) and construct a risk prediction model for prognosis and immunotherapy response of the patients based on these neutrophil subsets. METHODS: Single-cell and transcriptome data from PCa patients were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Neutrophil subsets in PCa were identified through unsupervised clustering, and their biological functions and effects on immune regulation were analyzed by functional enrichment, cell interaction, and pseudo-time series analyses. Lasso-Cox regression was utilized to construct a prognostic risk model based on the immunosuppressive neutrophil subsets, and survival analysis and ROC curve analysis were used to compare the prognosis of PCa patients with high and low risks stratified using this model. The relationship of the prognostic risk model with PCa immune infiltration and immune response was evaluated using CIBERSORT and TIDE scores. RESULTS: PCa tissues showed a significantly greater proportion of infiltrating neutrophils than the adjacent normal tissues (P<0.05). PCa-associated neutrophils could be clustered into two independent cell subsets: Neu_1 and Neu_2. Neu_2 cells exhibited highly enriched immunoregulatory functions and were highly differentiated and mature, with upregulated immunosuppressive cytokines such as TGFB1, ITGB2, and LGALS3. Based on the genetic characteristics of Neu_2 cell subsets, the prognostic risk model was constructed. The patients in the high-risk group identified by the model had a shorter biochemical recurrence time (P<0.05) and a higher proportion of Tregs and M2-TAMs cell infiltration (P<0.05) with a higher risk of immune rejection and poorer immune response scores. CONCLUSIONS PCa-associated neutrophils are highly heterogeneous. The prognostic risk model constructed based on the immunosuppressive neutrophil Neu_2 subset can effectively predict both the survival outcomes and immune response of PCa patients.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Prognosis ; Neutrophils/immunology* ; Immunotherapy

The increasing aging population and aging-associated diseases have become a global issue for decades. People over 65 show an increased prevalence and greater severity of periodontitis, which poses threats to overall health. Studies have demonstrated a significant association between aging and the dysfunction of neutrophils, critical cells in the early stages of periodontitis, and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion. Neutrophils differentiate and mature in the bone marrow before entering the circulation; during an infection, they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens. Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues. The impacts of aging on neutrophils' chemotaxis, anti-microbial function, cell activation, and lifespan result in impaired neutrophil functions and excessive neutrophil activation, which could influence periodontitis course. We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses. We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging. This review could help us better understand the pathogenesis of periodontitis, which could offer novel therapeutic targets for periodontitis.
Humans ; Neutrophils/immunology* ; Periodontitis/immunology* ; Aging/physiology*

Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Objective: To investigate the effects of derived neutrophil to lymphocyte ratio (dNLR) and lung immune prognostic index (LIPI) score on the overall survival (OS) of non-surgical elderly non-small cell lung cancer (NSCLC) patients. Methods: Clinical and pathological data of NSCLC patients in Hebei General Hospital from January 2014 to June 2018 were collected retrospectively. The dNLR value was calculated based on the results of blood routine before treatment, and the optimal cut-off value of dNLR was obtained by ROC curve. The patients were divided into low dNLR level group and high dNLR level group based on the optimal dNLR cut-off value. The groups were classified as good, intermediate and poor based on the LIPI score consisting of lactate dehydrogenase (LDH) and dNLR tested before treatment. The Kaplan-Meier method and Log rank test were used for survival analysis, and the Cox risk proportional regression model was used for analysis of prognostic influences. Results: The area under the ROC curve for dNLR predicting prognosis in non-surgical elderly NSCLC patients was 0.591 (95% CI: 0.491, 0.692; P=0.093). The optimal cut-off value for dNLR predicting prognosis in elderly NSCLC patients was 2.515, with a sensitivity of 45.5% and a specificity of 81.8%. The gender, BMI, pathological type and degree of tumor differentiation were associated with dNLR levels (P<0.05). The median survival times were 16 and 10 months for patients in the low dNLR level group (dNLR<2.51) and high dNLR level group (dNLR≥2.51), respectively (P<0.001), and 15, 10 and 6 months for patients with good, intermediate and poor LIPI scores, respectively (P<0.001). The age, gender, smoking, pathological type, tumor differentiation, clinical stage, BMI, dNLR level, LDH level and LIPI scores were all associated with patient prognosis (P<0.05), and age≥76 years, tumor differentiation and clinical stage Ⅲ and Ⅳ were independent factors influencing patient prognosis (P<0.05). Conclusion: No matter what treatment measures are taken, dNLR level and LIPI score are related to patients' prognosis, and non-surgical elderly NSCLC patients with high dNLR level and poor LIPI score before treatment have worse prognoses.
Aged ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; L-Lactate Dehydrogenase ; Lung Neoplasms/drug therapy* ; Lymphocytes/immunology* ; Neutrophils/immunology* ; Prognosis ; Retrospective Studies