Objective To investigate the expression of double-stranded DNA (dsDNA), citrulline histone 3 (CitH3), myeloperoxidase-DNA (MPO-DNA), IL-8 and IL-33 in plasma of patients with chronic obstructive pulmonary disease (COPD) and their clinical significance. Methods Forty patients with acute exacerbation COPD (AECOPD) who were hospitalized in The First Affiliated Hospital of Shihezi University School of Medicine from October 2020 to May 2021 were recruited in the AECOPD group, and recruited in the stable COPD group when they entered the stable stage. In the same period, forty healthy individuals were recruited in the control group. General informations including pulmonary function and peripheral blood were collected from each subject. Plasma levels of CitH3, MPO-DNA, interleukin (IL)-8 and IL-33 were measured by enzyme linked immunosorbent assay and plasma levels of dsDNA were measured by PicoGreen fluorescent dye quantitative analysis. Results The levels of dsDNA, CitH3, MPO-DNA, IL-8 and IL-33 in the AECOPD group were higher than those in the stable group and the control group, with statistical significance (P<0.05), and the levels of dsDNA, CitH3, MPO-DNA and IL-33 in the stable group were higher than those in the control group, with statistical significance (P<0.05) . The levels of CitH3, MPO-DNA, IL-33 and IL-8 in the AECOPD group were positively correlated with COPD assessment test (CAT) score. MPO-DNA and IL-8 were positively correlated with CAT score, MPO-DNA was negatively correlated with FEV1%pred, CitH3 was negatively correlated with FEV1/FVC. The levels of IL-8 and dsDNA, CitH3 were positively correlated with the levels of MPO-DNA in the AECOPD group, and positively correlated with the levels of IL-8 and dsDNA in the stable group, but not with CitH3 and MPO-DNA. The levels of IL-33 and IL-8, dsDNA, CitH3, MPO-DNA were positively correlated in the AECOPD group, but not in the stable group. Conclusions The levels of neutrophil extracellular traps (NETs), IL-8 and IL-33 in plasma of COPD patients were increased, and the levels of NETs were correlated with pulmonary function, CAT score, IL-33 and IL-8. NETs may be involved in the development of COPD.
Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither β2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.
ObjectiveTo investigate the regulation mechanism of neutrophils extracellular traps (NETs) on inflammatory diseases and to provide guidance for the treatment of related inflammatory diseases.MethodThe literatures about the relationship between NETs and inflammatory diseases were reviewed.ResultsNETs played an important role in sepsis, anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, acute pancreatitis, inflammatory bowel disease, and other inflammatory diseases, which were related to the development or activity of the diseases. By regulating the formation of NETs pathway, reducing the production of NETs, we could ultimately reduce the inflammation of the disease.ConclusionNETs is involved in the course of sepsis, ANCA-associated vasculitis, acute pancreatitis, inflammatory bowel disease, and other inflammatory diseases, but further investigation and clinical inflammatory verification are needed.
ObjectiveTo summarize the mechanism of neutrophil extracellular traps (NETs) in hepatic ischemia-reperfusion injury (HIRI) and the research progress in targeting NETs to reduce HIRI, providing valuable reference for reducing HIRI. MethodThe related literatures at home and abroad about the role of NETs in the pathogenesis of HIRI and target NETs to alleviate HIRI were retrieved and reviewed. ResultsHIRI usually appeared in the process of liver surgery and was a common clinical problem, which occured in situations such as liver surgery, organ transplantation, liver ischemia and so on. This kind of injury would lead to tissue necrosis, inflammatory response and oxidative stress, which was a major cause of hepatic dysfunction and multiple organ failure after hepatic surgery, greatly increases the complications and mortality after hepatic surgery. NETs played a crucial role in the aseptic inflammatory response induced by hepatic ischemia/reperfusion. During hepatic ischemia-reperfusion, neutrophils promoted inflammatory cascade reactions and cytokine storms by forming NETs, exacerbating damage caused by hepatic ischemia-reperfusion. At present, some experimental and clinical studies had shown that inhibiting the formation of NETs or eliminating the formed NETs could alleviate the hepatic ischemia-reperfusion injury and improve the prognosis. ConclusionsTargeting NETs may become a new method for treating hepatic ischemia-reperfusion injury. In the future, it is foreseeable that more experiments and clinical trials will be conducted on targeted NETs for the treatment of hepatic ischemia-reperfusion injury. And gradually establish more comprehensive and effective treatment strategies, thereby providing new ways to improve the prognosis of hepatic surgery patients in clinical practice.
Objective To investigate the correlation between the activation of peripheral blood neutrophil extracellular traps (NETs), oxidative stress levels, and the risk of developing acute respiratory distress syndrome (ARDS) in patients with multiple trauma, thereby providing a basis for the early prediction and intervention of post-traumatic ARDS. Methods This prospective cohort study enrolled 168 patients with multiple trauma admitted to our hospital between February 2023 and September 2025. Peripheral venous blood was collected within 24 hours of admission and on day 3 after treatment initiation. Plasma levels of NETs markers [neutrophil elastase (NE), citrullinated histone H3 (CitH3), myeloperoxidase (MPO)] and oxidative stress indicators [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx)] were measured. All patients were followed for 28 days post-admission and were categorized into ARDS and non-ARDS groups based on ARDS occurrence during follow-up. Univariate analysis, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were used to assess the correlation and predictive value of NETs and oxidative stress levels for ARDS risk. Results All 168 patients completed the 28-day follow-up. During follow-up, 42 patients (25.0%) developed ARDS. The ARDS group had significantly higher ISS scores, longer mechanical ventilation duration, and a higher proportion of surgical interventions, but lower Glasgow Coma Scale (GCS) scores at admission compared to the non-ARDS group (all P<0.05). At both 24 hours post-admission and on day 3 post-treatment, the ARDS group exhibited significantly higher levels of NE, CitH3, MPO, and MDA, and significantly lower levels of SOD and GPx compared to the non-ARDS group (all P<0.05). By day 3 post-treatment, levels of the aforementioned NETs markers and MDA had decreased, while SOD and GPx levels had increased in both groups; however, the magnitude of improvement was significantly smaller in the ARDS group (all P<0.05). Repeated measures ANOVA revealed statistically significant "time × group" interaction effects for NE, CitH3, MPO, MDA, SOD, and GPx levels (all P<0.05). Multivariate logistic regression analysis identified higher levels of NE, CitH3, MPO, and MDA at 24 hours post-admission as independent risk factors for ARDS, while higher levels of SOD and GPx at the same timepoint were independent protective factors (P<0.05). ROC analysis showed that the combination of plasma NE, CitH3, MPO, MDA, SOD, and GPx levels at 24 hours post-admission predicted ARDS risk with an AUC of 0.811 (95%CI: 0.728-0.895), which was significantly superior to the predictive efficacy of any single indicator alone (Z=3.344, 3.391, 3.069, 2.208, 2.794, 2.021, respectively; all P<0.05). Conclusion Enhanced peripheral blood NETs activation and oxidative stress imbalance are closely associated with an increased risk of ARDS in patients with multiple trauma. NE, CitH3, MPO, MDA, SOD, GPx are independent influencing factors for ARDS risk. Combined dynamic monitoring of these indicators can effectively enhance the predictive power for ARDS risk.