Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
Verlagsversion
DOI
PMC
 |
Open Access Gold |
|
möglich sobald bei der ZB eingereicht worden ist.
The eATP/P2×7R axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation.
Adv. Sci.:e2404661 (2024)
Exposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung-specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream-suspended particles. Therefore, exact knowledge about effects of engineered NPs within the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real-time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. Only PEG-amine-QDs, but not carboxyl-QDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space and was linked to cellular degranulation, TNF-α, and DAMP release into the circulation, particularly eATP. Stimulation of the ATP-gated receptor P2X7R induced expression of E-selectin on microvascular endothelium thereby mediating the neutrophilic immune response. Leukocyte integrins LFA-1 and MAC-1 facilitated adhesion and decelerated neutrophil crawling on the vascular surface. In summary, this study unravels the complex cascade of neutrophil recruitment during NP-induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP-based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Eatp P2x7 Axis ; Innate Immune Response ; Intravital Microscopy ; Lung ; Nanoparticles; Endothelial-cells; Alveolar Macrophage; Leukocyte Adhesion; Lung Inflammation; Extracellular Atp; P2x(7) Receptor; In-vitro; Mechanisms; Flow; Inhalation
ISSN (print) / ISBN
2198-3844
e-ISSN
2198-3844
Zeitschrift
Advanced science
Quellenangaben
Artikelnummer: e2404661
Verlag
Wiley
Verlagsort
Weinheim
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Lung Health and Immunity (LHI)
Institute of Experimental Genetics (IEG)
Institute of Lung Biology (LHI)
Institute of Experimental Genetics (IEG)
Institute of Lung Biology (LHI)
Förderungen
Projekt DEAL
European Union
European Union FET Proactive program
China Scholarship Council (CSC) fellowship
German Center for Diabetes Research (DZD)
German Federal Ministry of Education and Research (Infrafrontier grant)
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)
European Union
European Union FET Proactive program
China Scholarship Council (CSC) fellowship
German Center for Diabetes Research (DZD)
German Federal Ministry of Education and Research (Infrafrontier grant)
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)