NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. During formation of NETs, the nuclear membrane is disrupted by an as-yet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence microscopy revealed that 5 μM LL-37 significantly facilitated NET formation by primary human blood-derived neutrophils alone, in the presence of the classical chemical NET inducer PMA or in the presence of Staphylococcus aureus. Parallel assays with a random LL-37 fragment library indicated that the NET induction is mediated by the hydrophobic character of the peptide. The trans-localization of LL-37 towards the nucleus and the disruption of the nuclear membrane were visualized using confocal fluorescence microscopy. In conclusion, the present study demonstrates a novel role for LL-37 in the formation of NETs.
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http://dx.doi.org/10.1042/BJ20140778 | DOI Listing |
Neurobiol Dis
December 2024
Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Spain. Electronic address:
Obesity and metabolic disorders, such as metabolic syndrome (MetS) facilitate the development of neurodegenerative diseases and cognitive decline. Persistent neuroinflammation plays an important role in this process. Pleiotrophin (PTN) is a cytokine that regulates energy metabolism and high-fat diet (HFD)-induced neuroinflammation, suggesting that PTN could play an important role in the connection between obesity and brain alterations, including cognitive decline.
View Article and Find Full Text PDFEcotoxicol Environ Saf
December 2024
Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China; School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China. Electronic address:
Lead (Pb) exposure is widely acknowledged as a risk factor for cardiovascular diseases. Previous studies have established neutrophil involvement in Pb-induced cardiovascular injuries; however, the underlying mechanisms remain unclear. To address this knowledge gap, the binding targets of Pb in neutrophils and their roles in regulating neutrophil extracellular trap (NET) formation were investigated.
View Article and Find Full Text PDFFront 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 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.
J Am Chem Soc
December 2024
Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, and Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, Barcelona 08193, Spain.
Herein, we report how merging and clipping nets in metal-organic frameworks (MOFs) can be controlled in a single-crystal-to-single-crystal fashion using three different approaches─the merged net, clip-off chemistry, and linker reinstallation─to design and synthesize three- and two-merged net MOFs. Initially, we show the formation of three isoreticular three-merged net MOFs by linking a trimeric Sc cluster, Sc(μ-Ο)(-COO), with ditopic zigzag and tritopic linkers. The resulting MOFs exhibit three-merged edge-transitive nets─ + + ─for the first time.
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