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Neutrophil extracellular traps are potent antimicrobial weapons; however, their formation during sterile inflammation is detrimental, and the mechanism of induction is still unclear. Since advanced age is the primary clinical risk factor for poor outcomes in inflammatory diseases, we hypothesized that sterile stimuli, represented by mitochondria, would induce neutrophil extracellular trap formation in an age-dependent manner. Therefore, we analyzed induction of neutrophil extracellular traps in patients grouped according to age or immune status and observed that neutrophils from elderly patients responded to the presence of mitochondria with enhanced neutrophil extracellular trap formation. These neutrophil extracellular traps were also found to be more oxidized and exhibited higher resistance to DNase I degradation. Additionally, a higher concentration of residual neutrophil extracellular traps was detected in the plasma of the elderly. This plasma was capable of priming neutrophils through TLR9-mediated signaling, leading to further neutrophil extracellular trap formation, which was successfully inhibited with chloroquine. Finally, in a mouse model of mitochondria-induced acute lung injury, we observed that neutrophils from aged mice displayed impaired chemotactic activity but exhibited a trend of higher neutrophil extracellular trap formation. Thus, we propose that residual neutrophil extracellular traps circulating in the elderly preactivate neutrophils, making them more prone to enhanced neutrophil extracellular trap formation when exposed to mitochondria during sterile inflammation. Further investigation is needed to determine whether this vicious circle could be a suitable therapeutic target.
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http://dx.doi.org/10.1093/jleuko/qiad101 | DOI Listing |
Front Immunol
December 2024
Department of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, Japan.
Sepsis is characterized by a concomitant early pro-inflammatory response by immune cells to an infection, and an opposing anti-inflammatory response that results in protracted immunosuppression. The primary pathological event in sepsis is widespread programmed cell death, or cellular self-sacrifice, of innate and adaptive immune cells, leading to profound immunological suppression. This severe immune dysfunction hampers effective primary pathogen clearance, thereby increasing the risk of secondary opportunistic infections, latent viral reactivation, multiple organ dysfunction, and elevated mortality.
View Article and Find Full Text PDFCent Eur J Immunol
November 2024
Department of Respiratory Medicine, The Fourth Hospital of Changsha, Changsha, China.
Introduction: Neutrophil autophagy and neutrophil extracellular trap (NET) formation are closely related to asthma pathogenesis. Src homology domain 2-containing protein tyrosine phosphatase 2 (SHP2) is an important regulatory factor in airway remodeling in asthma. This study aimed to explore the molecular mechanisms of SHP2 in neutrophils.
View Article and Find Full Text PDFPlacenta
December 2024
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Department of Clinical Laboratory, The Laboratory of Placenta-related Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China, Jinan, Shandong, 250014, China. Electronic address:
Background: Inflammatory stress at the maternal-fetal interface plays an important role in the occurrence and development of preeclampsia(PE) caused by different etiologies. Many pathological neutrophil extracellular traps (NETs) at the maternal-fetal interface are believed to be among the main pathogenic factors leading to preeclampsia and the worsening of its symptoms. However, the underlying mechanism is largely unclear.
View Article and Find Full Text PDFJ Leukoc Biol
December 2024
Infectious and Immune Diseases Division, CHU de Québec Research Center, Laval University, Québec, QC, Canada.
Introduction: Granulocyte concentrates (GC) are leukocyte preparations enriched in neutrophils that can potentially save neutropenic patients from life-threatening, antimicrobial-resistant infections. The main challenge of GC transfusions is preserving the viability and antimicrobial activity of neutrophils beyond 24 h to reduce the logistical burden on collection centers and increase the availability of this cell therapy. Thus, the aim of this study was to explore extending the ex vivo viability and antimicrobial activity of GC neutrophils up to 72 h with a unique combination of the clinically-approved additives Plasma-Lyte, SAGM, AS-3 and Alburex.
View Article and Find Full Text PDFNeurologia (Engl Ed)
December 2024
Servicio de Neurología, Hospital Universitario Navarra, Pamplona, Navarra, Spain; RICORS-ICTUS, ISCIII, Madrid, Spain.
Introduction: Since mechanical thrombectomy has allowed ischemic stroke thrombi retrieval, its exhaustive study has involved a better knowledge of physiopathological processes implied in its formation.
Development: Thrombotic pathways involved in the different vascular beds shared common mechanisms conditioning difficulties in the identification of specific patterns associated with stroke etiology. Other factors as clot formation time, associated inflammatory status or activation of additional immune and coagulation pathways [Neutrophil extracellular traps (NETs) delivery, platelet aggregation, endothelial activation and VonWillebrand Factor release] have been described as determinants in thrombus characteristics.
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