Neutrophil extracellular traps in homeostasis and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

---

Neutrophil extracellular traps potentiate effector T cells via endothelial senescence in uveitis

JCI Insight, Journal Year: 2025, Volume and Issue: 10(2)

Published: Jan. 22, 2025

Autoimmune uveitis (AU) is a sight-threatening ocular autoimmune disorder that often manifests as retinal vasculitis. Increased neutrophil infiltration around vessels has been reported during the progression of AU, while how they function not fully recognized. Neutrophil extracellular traps (NETs), produced by activated neutrophils, have suggested to be detrimental in diseases. Here, we found NETs were elevated patients with active and this was verified an experimental AU (EAU) mouse model. Depletion neutrophils or degradation deoxyribonuclease-I (DNase I) could decrease CD4+ effector T cell (Teff) retina spleen alleviate EAU. Moreover, expression adhesion molecules, selectin, antigen-presenting molecules EAU microvascular endothelial cells (RMECs) cocultured NETs. The stimulated RMECs further facilitated adhesion, activation, differentiation into Teffs. Mechanistically, trigger RMEC activation hastening senescence through cyclic GMP-AMP synthase (cGAS)/stimulator interferon genes (STING) pathway. Slowing down inhibiting cGAS/STING pathway reduces cells. These results suggest deleterious role AU. Targeting would offer effective therapeutic method.

Language: Английский

---

A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1464 - 1464

Published: Jan. 25, 2024

Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation treatment of ARDS remains major research focus. There are various causes ARDS, among which pneumonia non-pulmonary sepsis most common. Trauma blood transfusion can also cause ARDS. In aggregation infiltration neutrophils in lungs have great influence on development disease. Neutrophils regulate inflammatory responses through pathways, release neutrophil extracellular traps (NETs) is considered to be one important mechanisms. NETs mainly composed DNA, histones, granuloproteins, all mediate downstream signaling pathways that activate responses, generate immune clots, damage surrounding tissues. At same time, components promote formation NETs, thus forming vicious cycle continuously aggravates progression associated with cytokine storms balance. Since DNA main component DNase I viable drug for removing NETs. Other therapeutic methods inhibit worthy further exploration. This review discusses mechanism Understanding association between may help develop new perspectives

Language: Английский

---

Local complement activation and modulation in mucosal immunity

Mucosal Immunology, Journal Year: 2024, Volume and Issue: 17(4), P. 739 - 751

Published: June 4, 2024

Language: Английский

---

Neutrophil Extracellular Traps in Cardiovascular and Aortic Disease: A Narrative Review on Molecular Mechanisms and Therapeutic Targeting

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3983 - 3983

Published: April 3, 2024

Neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, are released by neutrophils in response to pathogens but also recognized for their involvement a range pathological processes, including autoimmune diseases, cancer, cardiovascular diseases. This review explores the intricate roles NETs different conditions such as thrombosis, atherosclerosis, myocardial infarction, COVID-19, particularly pathogenesis abdominal aortic aneurysms. We elucidate mechanisms underlying NET formation function, provide foundational understanding biological significance, highlight contribution inflammation, tissue remodeling vascular disease. Therapeutic strategies preventing release compared with approaches targeting components formed Current limitations potential avenues clinical translation anti-NET treatments discussed.

Language: Английский

---

The complement system: A key player in the host response to infections

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(11)

Published: Aug. 27, 2024

Abstract Infections are one of the most significant healthcare and economic burdens across world as underscored by recent coronavirus pandemic. Moreover, with increasing incidence antimicrobial resistance, there is an urgent need to better understand host–pathogen interactions design effective treatment strategies. The complement system a key arsenal host defense response pathogens bridges both innate adaptive immunity. However, in contest between mechanisms, not always victorious. Pathogens have evolved several approaches, including co‐opting regulators evade complement‐mediated killing. Furthermore, deficiencies proteins, genetic therapeutic, can lead inefficient pathogen eradication, rendering more susceptible certain infections. On other hand, overwhelming infection provoke fulminant activation uncontrolled inflammation potentially fatal tissue organ damage. This review presents overview critical aspects complement‐pathogen during discusses perspectives on designing therapies mitigate dysfunction limit injury.

Language: Английский

---

A mimetic peptide of ACE2 protects against SARS-CoV-2 infection and decreases pulmonary inflammation related to COVID-19

Antiviral Research, Journal Year: 2024, Volume and Issue: 229, P. 105968 - 105968

Published: July 14, 2024

Language: Английский

---

Therapeutic targeting of alternative pathway and C5 but not C5a protects from disease development in a preclinical model of autoimmune blistering dermatosis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Epidermolysis Bullosa Acquisita (EBA) is an autoimmune blistering dermatosis characterized by autoantibodies (AAbs) against type VII collagen (COL7) located at the dermal epidermal junction (DEJ). Local complement activation drives C5a generation associated with neutrophil recruitment and resulting in skin lesions inflammation. Here we tested impact of C5a/C5adesArg, C5 or combined alternative pathway (AP) targeting on disease development inflammation a preclinical mouse model mimicking effector phase EBA. C57BL/6 mice were treated subcutaneously purified rabbit anti-mouse-COL7 IgG presence IgG1 mAbs directed murine C5a/C5adesArg (M031), (mBB5.1), bifunctional protein comprising mBB5.1 fused to active fragment AP inhibitor factor H (M014) isotype control mAb. Formation was evaluated 12 days every other day. On day 12, DEJ separation, AAb C3b deposition infiltration assessed. Isotype IgG1-treated developed first 4 peaking 12. Prophylactic treatment either M031 M014 markedly reduced lesions, dermal/epidermal separation recruitment. Surprisingly, AP/C5 inhibition but not C5a/C5adesArg-targeting setting therapeutic treatment. affected Importantly, direct comparison isolated vs. revealed that earlier more pronounced than mBB5.1. Our findings identify C5/AP as novel option for dermatoses.

Language: Английский

---

Pathological roles of NETs-platelet synergy in thrombotic diseases: From molecular mechanisms to therapeutic targeting

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 159, P. 114934 - 114934

Published: May 25, 2025

Language: Английский

---

The multi-herbal decoction SH003 alleviates LPS-induced acute lung injury by targeting inflammasome and extracellular traps in neutrophils

Phytomedicine, Journal Year: 2024, Volume and Issue: 133, P. 155926 - 155926

Published: July 30, 2024

Language: Английский

---