How Neutrophils Shape the Immune Response: Reassessing Their Multifaceted Role in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17583 - 17583

Published: Dec. 18, 2023

Neutrophils are the most abundant of circulating immune cells and first to be recruited sites inflammation. a heterogeneous group from which derived extracellular traps (NETs), reactive oxygen species, cytokines, chemokines, immunomodulatory factors, alarmins that regulate recruitment phenotypes neutrophils, macrophages, dendritic cells, T B cells. In addition, cytokine-stimulated neutrophils can express class II major histocompatibility complex internal machinery necessary for successful antigen presentation memory CD4+ This may relevant in context vaccine memory. thus emerge as orchestrators responses play key role determining outcome infections, efficacy, chronic diseases like autoimmunity cancer. review aims provide synthesis current evidence regards these functions homeostasis disease.

Language: Английский

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Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2406 - 2406

Published: Feb. 18, 2024

Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration stem cell-derived exosomes can mitigate injuries. While demonstrated ability modulate microglial reactions and enhance blood-brain barrier integrity, their impact on deactivation, especially context NETs, remains poorly understood. This study aims investigate effects MSC-derived exosomes, with specific focus NET formation, elucidate associated molecular mechanisms. Exosomes were isolated from cell supernatants amnion-derived mesenchymal cells using ultracentrifugation method. injuries induced Sprague-Dawley rats (9 weeks old) clip model, 100 μg 1 mL PBS or alone intravenously administered 24 h post-injury. Motor function was assessed serially up 28 days following injury. On Day 3 28, spinal specimens analyzed evaluate extent formation NETs. Flow cytometry employed examine circulating Exogenous miRNA electroporated into effect inflammatory formation. Finally, biodistribution 64Cu-labeled animal positron emission tomography (PET). Rats treated exhibited substantial improvement motor recovery reduction size. Notably, there significant decrease infiltration within cord, as well forming NETs circulation. In vitro investigations indicated accumulated vicinity nuclei activated neutrophils, miR-125a-3p mimic significantly diminished while inhibitor reversed effect. PET studies revealed that, although majority transplanted sequestered liver spleen, notably high quantity detected damaged when compared normal rats. play pivotal alleviating injury, part through deactivation via miR-125a-3p.

Language: Английский

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Neutrophils in glioma microenvironment: from immune function to immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 8, 2024

Glioma is a malignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important member microenvironment (TME), widely distributed in circulation. Recently, discovery cranial-meningeal channels and intracranial lymphatic vessels has provided new insights into origins neutrophils CNS. Neutrophils brain may originate more from skull adjacent vertebral bone marrow. They cross blood-brain barrier (BBB) under action chemokines enter parenchyma, subsequently migrating to glioma TME undergoing phenotypic changes upon contact with cells. Under glycolytic metabolism model, show complex dual functions different stages cancer progression, including participation immune suppression, anti-tumor effects gliomas. Additionally, interact other cells, playing crucial role immunotherapy. Targeting be novel generation immunotherapy improve efficacy treatments. This article reviews molecular mechanisms infiltrating external environment, detailing origin, functions, classifications, targeted therapies context glioma.

Language: Английский

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Neutrophil extracellular traps and long COVID

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 27, 2023

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by significant number survivors. The underlying pathophysiology COVID has become topic intense research discussion. While chronic inflammation in received considerable attention, the role neutrophils, which are most abundant all immune cells and primary responders to inflammation, been unfortunately overlooked, perhaps due their short lifespan. In this review, we discuss emerging neutrophil extracellular traps (NETs) persistent inflammatory response observed patients. We present early evidence linking persistence NETs pulmonary fibrosis, cardiovascular abnormalities, neurological dysfunction COVID. Several uncertainties require investigation future studies. These include mechanisms SARS-CoV-2 brings about sustained activation phenotypes after infection resolution; whether heterogeneity neutrophils seen acute persists into phase; presence autoantibodies can induce protect them from degradation; exert differential, organ-specific effects; specifically NET components contribute pathologies, such fibrosis; senescent drive formation through pro-inflammatory secretome Answering these questions may pave way for development clinically applicable strategies targeting NETs, providing relief health crisis.

Language: Английский

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Macrophages coordinate immune response to laser-induced injury via extracellular traps

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: March 18, 2024

Abstract Background Retinal degeneration results from disruptions in retinal homeostasis due to injury, disease, or aging and triggers peripheral leukocyte infiltration. Effective immune responses rely on coordinated actions of resident microglia recruited macrophages, critical for tissue remodeling repair. However, these phagocytes also contribute chronic inflammation degenerated retinas, yet the precise coordination response damage remains elusive. Recent investigations have demonstrated that phagocytic cells can produce extracellular traps (ETs), which are a source self-antigens alter response, potentially lead injury. Methods Innovations experimental systems facilitate real-time exploration cell interactions dynamic responses. We integrated vivo imaging with ultrastructural analysis, transcriptomics, pharmacological treatments, knockout mice elucidate role their modulation local inflammatory through (ETs). Deciphering mechanisms is essential developing novel enhanced immunotherapeutic approaches redirect specific maladaptive towards favorable wound healing retina. Results Our findings underscore pivotal innate cells, especially macrophages/monocytes, regulating repair inflammation. The absence neutrophil macrophage infiltration aids parenchymal integrity restoration, while depletion, particularly impedes vascular recovery. demonstrate when retina, release chromatin granular proteins, forming ETs. Furthermore, inhibition ETosis support repair, surpassing effects blocking recruitment. Simultaneously, reshapes causing neutrophils, helper, cytotoxic T-cells be restricted primarily superficial capillary plexus instead reaching damaged photoreceptor layer. Conclusions data offer insights into immunity's responding help innovative shift beneficial regeneration.

Language: Английский

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Microenvironmental regulation of tumor-associated neutrophils in malignant glioma: from mechanism to therapy

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Sept. 16, 2024

Glioma is the most common primary intracranial tumor in adults, with high incidence, recurrence, and mortality rates. Tumor-associated neutrophils (TANs) are essential components of microenvironment (TME) glioma play a crucial role cell proliferation, invasion proneural-mesenchymal transition. Besides interactions between TANs cells, multi-dimensional crosstalk other within TME have been reported to participate progression. More importantly, several therapies targeting developed relevant preclinical clinical studies conducted cancer therapy. In this review, we introduce origin functions malignant behaviors glioma, highlighting microenvironmental regulation TANs. Moreover, focus on summarizing TANs-targeted methods therapy, aiming provide insights into mechanisms therapeutic opportunities microenvironment.

Language: Английский

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Blood-brain barrier permeability for the first 24 hours in hypoxic-ischemic brain injury following cardiac arrest

Resuscitation, Journal Year: 2024, Volume and Issue: 198, P. 110150 - 110150

Published: Feb. 23, 2024

Language: Английский

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The Diagnostic Value of Plasma NETs Levels and iCEB in Silent Myocardial Ischemia in Maintenance Hemodialysis Patients

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 847 - 862

Published: Jan. 1, 2025

This study evaluated the diagnostic value of plasma Neutrophil extracellular traps (NETs) levels and index cardiac electrophysiological balance (iCEB) in identifying silent myocardial ischemia (SMI) maintenance hemodialysis (MHD) patients. cross-sectional observational involved patients receiving MHD treatment. Data were collected on coronary angiography performed our hospital from February 2023 to 2024. Patients diagnosed with via but without obvious symptoms grouped as SMI group, while those control group. Plasma NETs assessed using markers indicative components including double-stranded DNA (dsDNA), circulating free (cfDNA) myeloperoxidase, iCEB (QT/QRS) electrocardiographic findings obtained. Additionally, echocardiographic parameters, inflammatory markers, biomarkers analyzed. Receiver operating characteristic (ROC) analysis employed evaluate accuracy SMI. A total 114 included, 79 participants group 35 The exhibited significantly elevated associated (dsDNA(37.89±4.55 vs 31.64±5.32, P<0.001), cfDNA(11.27±2.03 8.91±1.84, MPO-DNA(23.69±4.01 17.52±3.41, P<0.001)), well higher compared group(56.45±7.67 45.89±6.23, P<0.001). Furthermore, electrocardiography findings, showed significant differences between two groups. ROC demonstrated potential accuracies iCEB, an area under curve (AUC) 0.908, sensitivity 0.987, specificity 0.829 for highlights combined patients, providing valuable insights into early detection risk stratification strategies this population.

Language: Английский

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Preliminary evidence of immune infiltration and neutrophil degranulation in peripheral blood of non-obese OSA patients related to cognitive decline

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 28, 2025

Obstructive sleep apnea (OSA) patients have varying degrees of cognitive impairment, but the specific pathogenic mechanism is still unclear. Meanwhile, poor compliance with continuous positive airway pressure (CPAP) in OSA prompts better solutions. This study aimed to identify differentially expressed genes between non-obese and healthy controls, explore potential biomarkers associated impairment. Cohorts control (n = 20) non-obese, treatment-naïve were recruited. We collected their peripheral blood mononuclear cells neutrophils, performances evaluated by Montreal Cognitive Assessment (MoCA). The identified bioinformatic analysis confirmed PCR. Imbalanced immune cell proportions assessed Cibersort. Biomarkers related enriched cellular pathways measured ELISA. showed a significant decline overall function higher daytime sleepiness scores. Multiple signaling cohort, including upregulation neutrophil-degranulation. Increased monocyte proportion decreased NK figured out. relevant genes, upregulated defensin alpha 4 (DEFA4), haptoglobin (HP), survivin (BIRC5), suppressed interferon gamma (IFNG) expression detected. relative DEFA4 was significantly correlated MoCA score parameters. such as myeloperoxidase (MPO), H2O2, lipocalin-2, representatives neutrophils' activation, elevated group. data demonstrated correlation MPO oxygen desaturation index (ODI) negative lowest saturation (LSaO2). level Lipocalin-2 positively apnea-hypopnea (AHI) ODI negatively LSaO2 score. also observed H2O2 mean (MSaO2). Degranulation neutrophils activated without other complications. process severity implying its role pathogenesis.

Language: Английский

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Hypothesis on the role of cholesterol crystals in spontaneously ruptured aortic plaques: Potential triggers for inflammation and systemic effects

American Heart Journal Plus Cardiology Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 100507 - 100507

Published: Jan. 1, 2025

Cholesterol crystals (CCs) are a key component of atherosclerotic plaques and play pivotal role in plaque progression, rupture, the resulting inflammatory responses. CCs emboli trigger proinflammatory cytokines which can potentially lead to organ damage. Spontaneously ruptured aortic (SRAPs) frequently observed via non-obstructive general angioscopy (NOGA) patients with or suspected coronary artery disease. The release from SRAPs activate innate immune system induce neutrophil extracellular trap (NET) formation, further exacerbating inflammation. Inflammation levels vary, interleukin (IL)-6 ratio may reflect degree Systemic inflammation induced by contribute conditions that cerebral infarction, chronic kidney effects anti-inflammatory drugs, including IL-6 inhibitors, IL-1β colchicine, be evaluated measuring SRAPs. This review examined immunity mechanisms associated sampled NOGA discussed their systemic impact potential therapeutic strategies.

Language: Английский

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