Nanoparticles containing intracellular proteins modulate neutrophil functional and phenotypic heterogeneity

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 22, 2025

Neutrophils are rapidly recruited to sites of infection, injury, or immune complexes. Upon arrival, they initiate degranulation, release reactive oxygen species (ROS), and/or nuclear extracellular traps (NETs) eliminate invading microorganisms, clear debris, remove abnormal immunoglobulins. While these processes ideally trigger healing and a return balance, overshooting neutrophil function can lead life-threatening infections such as sepsis persistent inflammation observed in various autoimmune diseases. However, recent evidence highlights phenotypic functional heterogeneity neutrophils that extends well beyond their traditional - potentially harmful- role first responders. For example, regulate ongoing by modulating macrophage through efferocytosis, T cell responses antigen presentation the cytokines. The factors induce differentiation into activating regulatory phenotypes remain poorly defined. Here, we hypothesize intracellular components have been released space could contribute neutrophils. To find out, used nanoparticles composed proteins (cell-derived nanoparticles, CDNPs) analyzed effects on cultured murine bone marrow (BMN). We CDNPs activate BMN transiently with an increase expression CD11b without triggering classical effector functions. Additionally, secretion IL-10, shift PMA-induced death toward apoptosis, CD80. Mechanistically, our findings indicate 26% BMNs ingest CDNPs. These preferentially express CD54+, fail migrate CXCL12, exhibit diminished LPS, undergo apoptosis. data identify biomaterials modulate behavior fine-tuning

Language: Английский

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Pulmozyme Ameliorates LPS-Induced Lung Fibrosis but Provokes Residual Inflammation by Modulating Cell-Free DNA Composition and Controlling Neutrophil Phenotype

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 298 - 298

Published: Feb. 17, 2025

Pulmonary fibrosis, a chronic progressive lung disorder, can be the result of previous acute inflammation-associated injury and involves wide variety inflammatory cells, causing deposition extracellular matrix (ECM) components in lungs. Such is often associated with excessive neutrophil function formation DNA networks lungs, which are also some most important factors for fibrosis development. Acute subsequent was initiated C57Bl/6 mice by single intranasal (i.n.) administration LPS. Starting from day 14, human recombinant DNase I form Pulmozyme topical instilled i.n. twice week at dose 50 U/mouse. Cell-free (cfDNA), activity, cell content were analyzed blood serum bronchoalveolar lavage fluid (BALF). Inflammatory fibrotic changes tissue evaluated histological analysis. The gene expression profile spleen-derived neutrophils RT-qPCR. We demonstrated that significantly reduced connective expansion However, despite reliable antifibrotic effect, complete resolution inflammation respiratory system treated not achieved, possibly due to enhanced granulocyte recruitment nuclear/mitochondrial cfDNA balance BALF. Moreover, introduction caused enrichment population those an unusual phenotype, combining pro-inflammatory anti-inflammatory features, maintain inflammation. considered promising drug management; however, therapy may accompanied residual

Language: Английский

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Tumor- and Fibroblast-Derived Cell-Free DNAs Differently Affect the Progression of B16 Melanoma In Vitro and In Vivo

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5304 - 5304

Published: May 13, 2024

It is widely postulated that the majority of pathologically elevated extracellular or cell-free DNA (cfDNA) in cancer originates from tumor cells; however, evidence has emerged regarding significant contributions other cells microenvironment. Here, effect cfDNA originating murine B16 melanoma and L929 fibroblasts on was investigated. found cfDNAL929 increased viability migration properties vitro their invasiveness vivo. In contrast, cfDNAB16 exhibited a negative cells, reducing vitro, which vivo led to decreased size metastasis number. shown cell treatment with both cfDNAs resulted an increase expression genes encoding DNases oncogenes Braf, Kras, Myc. cfDNAL929-treated were experience oxidative stress. Gene changes case are well correlated observed decrease proliferation cells. The obtained data may indicate possible involvement fibroblast microenvironment progression and, potentially, formation new foci due transformation normal

Language: Английский

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Two transcriptionally and functionally distinct waves of neutrophils during mouse acute liver injury

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(7)

Published: June 19, 2024

Background: Neutrophils are key mediators of inflammation during acute liver injury (ALI). Emerging evidence suggests that they also contribute to resolution and tissue repair. However, the different neutrophil subsets involved in these processes their kinetics undefined. Herein, we characterized heterogeneity ALI. Methods: We used carbon tetrachloride model ALI employed flow cytometry, imaging, quantitative RT-PCR characterize intrahepatic neutrophils necroinflammatory early late repair phases wound healing response FACS sorted at time points examined transcriptional profiles using RNA-sequencing. Finally, evaluated protein translation, mitochondrial function metabolism, reactive oxygen species content, extracellular traps generation. Results: detected 2 temporarily distinct waves (1) necroinflammation (at 24 hours after injury) (2) 72 hours). Early were proinflammatory, by: upregulation inflammatory cytokines, activation noncanonical NF-κB pathway, (3) reduction (4) decreased oxidative phosphorylation, (5) higher propensity generate traps. In contrast, prorepair enriched genes pathways associated with angiogenesis. proinflammatory by expression a short isoform C-X-C chemokine receptor 5, while 4. Conclusions: This study underscores phenotypic functional dual role

Language: Английский

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Identification of neutrophil extracellular traps (NETs)-related molecular clusters in prostate cancer: Implications for predicting biochemical recurrence

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 146, P. 113908 - 113908

Published: Dec. 28, 2024

Language: Английский

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Tbp and Hprt1 Are Appropriate Reference Genes for Splenic Neutrophils Isolated from Healthy or Tumor-Bearing Mice

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2571 - 2571

Published: Nov. 10, 2024

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