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GSDMD-NETs in patients with sepsis-induced coagulopathy and their interaction with glycocalyx damage.

INTRODUCTION: Neutrophil extracellular traps (NETs) play a critical role in inflammation and coagulation imbalance. Recent studies have demonstrated that activation of gasdermin D (GSDMD) protein and its pore-forming activity are essential drivers of NET generation. This study investigated the association between GSDMD-NETs axis activation and sepsis-induced coagulopathy (SIC), as well as the potential association with glycocalyx damage. MATERIALS AND METHODS: A prospective cohort of 70 sepsis patients (35 with SIC, 35 non-SIC) admitted to a respiratory intensive care unit was analyzed. This …

NETs-CD44-IL-17A Feedback Loop Drives Th17-Mediated Inflammation in Behçet's Uveitis.

Behçet's uveitis (BU) is a severe ocular manifestation of Behçet's disease, typically accompanied by abnormal neutrophil infiltration and hyperactivation. However, the underlying causes of excessive neutrophil extracellular traps (NETs) production and mechanisms by which NETs contribute to the pathogenesis of BU remain incompletely understood. Neutrophils from BU patients exhibit a higher propensity for NETs release compared to healthy controls. In the experimental autoimmune uveitis (EAU), neutrophils are observed to exert pro-inflammatory effects through NETs. Clearing NETs can inhibit T hel…

Er Miao San and its main components phellodendrine and atractylenolide-I exert anti-rheumatoid arthritis effects by inhibiting PAD4 and thereby reducing the formation of NETs.

BACKGROUND: Er Miao San (EMS) is an important Chinese herbal formula for the treatment of damp-heat underflow syndrome, and has been clinica … d and Phorbol 12-myristate 13-acetate (PMA) stimulated the formation of neutrophils form neutrophil extracellular traps (NETs). The effects of EMS and its main active components PHE and ATL-I on the formation of NETs were assessed by molecular docking, immunofluorescence, western blotting, and ELISA. RESULTS: The results showed that EMS reduced inflammation scores, …

Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETos

Functional plasticity shapes neutrophil response to Leishmania major infection in susceptible and resistant strains of mice.

Neutrophils rapidly infiltrate sites of infection and possess several microbicidal strategies, such as neutrophil extracellular traps release and phagocytosis. Enhanced neutrophil infiltration is associated with higher susceptibility to Leishmania infection, but neutrophil effector response contribution to this phenotype is uncertain. Here, we show that neutrophils from susceptible BALB/c mice (B/c) produce more NETs in response to Leishmania major than those from resistant C57BL/6 mice (B6), which are more phagocytic. The absence of neutrophil elastase contributes to phagocytosis regulation. …

Resveratrol and tetrahydroisoquinoline effects on neutrophil sensitivity to NETosis formation in low-risk essential thrombocythemia patients.

INTRODUCTION: Recent studies scrutinize how NETosis (a unique cell death mechanism of neutrophil), impacts thrombosis patients with essential thrombocythemia (ET). This research evaluates the susceptibility of ET neutrophils to form NETs and tests two potential inhibitors, resveratrol (RSV) and tetrahydroisoquinoline (THIQ), in vitro. METHODS: Platelet-rich plasma from low-risk ET patients was used, along with neutrophils from both patients and controls. NET formation assays, with or without RSV and THIQ treatment after LPS stimulation, were conducted in a CO2 incubator. Evaluation included f

Dapsone Alters Phenotypical and Functional Properties of Human Neutrophils In Vitro.

Dapsone is a sulfone used in treating inflammatory skin conditions. Despite its widespread dermatological use, the pharmacological actions of dapsone remain poorly understood. Here, we examined how different aspects of neutrophil functions are affected by dapsone. Peripheral blood neutrophils from healthy donors were stimulated with phorbol-12-myristate-13-acetate (PMA), N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), or calcium ionophore (CaI) or primed with cytokines prior to stimulation, in the presence of different concentrations of dapsone (from 10 to 50 µg/mL), followed by analyses

Spontaneous Lethal Outbreak of Influenza A Virus Infection in Vaccinated Sows on Two Farms Suggesting the Occurrence of Vaccine-Associated Enhanced Respiratory Disease with Eosinophilic Lung Pathology.

Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of infiltrating eosinophils. The purpose of this study was to characterize these lung lesions with special emphasis on the phenotypes of inflammatory cells, the presence of eosinophilic peroxidase (EPO), and neutrophil extracellular traps (NETs). The number of Sirius red-stained eosinophils was s…

A review on gout: Looking back and looking ahead.

Gout is a metabolic disease caused by the deposition of monosodium urate (MSU) crystals inside joints, which leads to inflammation and tissue damage. Increased concentration of serum urate is an essential step in the development of gout. Serum urate is regulated by urate transporters in the kidney and intestine, especially GLUT9 (SLC2A9), URAT1 (SLC22A12) and ABCG. Activation of NLRP3 inflammasome bodies and subsequent release of IL-1β by monosodium urate crystals induce the crescendo of acute gouty arthritis, while neutrophil extracellular traps (NETs) are considered to drive the self-resolvi…

Aged neutrophils form mitochondria-dependent vital NETs to promote breast cancer lung metastasis.

BACKGROUND: Neutrophils-linked premetastatic niche plays a key role in tumor metastasis, but not much is known about the heterogeneity and d … ents and mice models (4T1 and MMTV-PyMT) by flow cytometry. The ability of Naged to form neutrophil extracellular traps (NETs) and promote tumor metastasis in patients and mice was determined by polychromatic immunohistochemistry, scanning electron microscopy and real-time video detection. Furthermore, the differences among tumor-associated Naged, Non-Naged and infla …

An Update on the Pathogenic Role of Neutrophils in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease.

Neutrophils are innate immune phagocytes that play a key role in immune defense against invading pathogens. The main offensive mechanisms of neutrophils are the phagocytosis of pathogens, release of granules, and production of cytokines. The formation of neutrophil extracellular traps (NETs) has been described as a novel defense mechanism in the literature. NETs are a network of fibers assembled from chromatin deoxyribonucleic acid, histones, and neutrophil granule proteins that have the ability to kill pathogens, while they can also cause toxic effects in hosts. Activated neutrophils with NET…

Role of Neutrophils in Psoriasis.

Psoriasis is a common inflammatory disease that can involve the skin, joints, or both. The abnormalities of innate immunity play crucial roles in the pathogenesis of psoriasis. Neutrophils are the most abundant leukocytes in the circulation. Emerging evidences have demonstrated that neutrophils may play a role in autoimmune diseases. The neutrophil-to-lymphocyte ratio (NLR), the activity of neutrophils, and the number of NETotic cells were significantly higher in psoriasis patients compared to healthy controls. The number of low-density granulocytes (LDGs) in the blood of psoriasis patients wa

Human Neutrophils Use Different Mechanisms To Kill Aspergillus fumigatus Conidia and Hyphae: Evidence from Phagocyte Defects.

Neutrophils are known to play a pivotal role in the host defense against Aspergillus infections. This is illustrated by the prevalence of Aspergillus infections in patients with neutropenia or phagocyte functional defects, such as chronic granulomatous disease. However, the mechanisms by which human neutrophils recognize and kill Aspergillus are poorly understood. In this work, we have studied in detail which neutrophil functions, including neutrophil extracellular trap (NET) formation, are involved in the killing of Aspergillus fumigatus conidia and hyphae, using neutrophils from patients wit

Изменения в профилях нейтрофильных мРНК в множестве склерозов и идентификации потенциальных генов для дальнейшего исследования.

ВВЕДЕНИЕ: Множественный склероз (MS) является хроническим и изнурительным воспалительным заболеванием центральной нервной системы (КНС), характеризующимся демиэлированием и нейродегенерацией. Появляющиеся данные свидетельствуют о наличии нейтрофилов в патогенезе MS, особенно в рамках таких процессов, как образование нейтрофильных внеклеточных ловушек (NETs) и дегрануляция, которые могут усилить воспаление и автонепроницаемость. МЕТОДЫ: Секвенирование последовательности периферийных нейтрофилов крови у пациентов с синдромом MS и здоровый контроль выявили дифференциально выраженные гены (DEGs).

Совпадение в аннотации оригинала
INTRODUCTION: Multiple sclerosis (MS) is a chronic and debilitating inflammatory disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Emerging evidence implicates neutrophils in MS pathogenesis, particularly through processes like neutrophil extracellular traps (NETs) formation and degranulation, which may exacer…

Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection.

UNLABELLED: Aspergillus flavus and Fusarium sp. are primary causative agents of keratitis that results in corneal tissue damage leading to v … glycosylation pattern after infection. Complement system proteins, proteins specific for neutrophil extracellular traps and proteins involved in would healing were found only in the patient tear. The presence of these innate immune system proteins in the tear film of patients supports the previous data indicating the involvement of neutrophil and complement pathways …

Targeting NETosis in the Lung: Respiratory Delivery of Neutrophil-Specific NEBP-Liposomes for Enhanced Therapy of Acute Lung Injury.

The activation, adhesion, and migration of neutrophils are one of the main reasons for the progression of acute lung injury (ALI) and a new … (N-Lip@A) that can be administered via the respiratory tract to inhibit the formation of neutrophil extracellular traps, aiming to provide a rapid, efficient, and precise intervention strategy for ALI. N-Lip@A liposomes were synthesized by the traditional thin-film hydration method. Cell immunofluorescence and scanning electron microscopy observations indicated that …

PAD4+ neutrophils promote hepatic stellate cell activation and accelerate MASH fibrosis progression viaNET-DNA/TAOK1/MAPK pathways.

Neutrophils play a pivotal role in the progression of metabolic dysfunction-associated steatohepatitis (MASH) by mediating inflammatory resp … serving as key drivers in MASH progression. Mechanistically, PAD4+ neutrophils generate neutrophil extracellular traps (NETs) and activate hepatic stellate cells via the TAOK1-dependent MAPK signaling pathway. Inhibition of PAD4+ neutrophils in vivo attenuated the progression of liver fibrosis without exacerbating liver injury. Collectively, these findings elucidate …

The DanRI regulatory system in uropathogenic Escherichia coli subverts neutrophil responses.

Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTIs). To establish an infection, UPEC must evade infiltrating neutrophils and their antimicrobial neutrophil extracellular traps (NETs). In this study, we identify a previously uncharacterized two-gene regulatory system within the pathogenicity island PAIUTI89II, which we named DanRI (defense against neutrophil regulator and inhibitor). DanRI is induced by nucleosomes present in NETs and enables UPEC to suppress neutrophil responses by attenuating reactive oxygen species production and subsequent NET forma…

Pathological Effects of NETs: Seed and soil hypothesis for inflammation spread by primed neutrophils.

The ability of activated neutrophils to release decondensed chromatin as neutrophil extracellular traps (NETs) in response to stimuli is conserved throughout evolution. While NETs support host defense by forming physical barriers against microbes, their toxicity can cause tissue damage. Large NET networks, generated through the activation of the NLRP3 inflammasome, the citrullinating enzyme PAD4, and neutrophil-derived enzymes, are central to the pathogenesis of numerous diseases. Chronic disorders often originate in a localized site, for example the joints in rheumatoid arthritis, or followin…

[Complement-coagulation crosstalk in immunothrombosis].

Venous thrombosis is initiated by endothelial cell activation triggered by reduced blood flow and venous stasis. Innate immune cells (neutrophils and monocytes) and platelets adhere to activated endothelial cells via P-selectin and von Willebrand factor multimers, respectively. Platelet activation involves integrin activation, P-selectin expression, and the release of ADP, polyphosphates, and soluble complement regulators. Neutrophils bind to the activated platelets and endothelial cells and release neutrophil extracellular traps. Activated monocytes express tissue factor. The interplay of the…