Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

Abstract

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.

People
Li, Chenxi
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Liu, Qiongliang
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Han, Lianyong
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Zhang, Haiyun
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Immler, Roland
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Rathkolb, Birgit
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Secklehner, Judith
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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de Angelis, Martin Hrabe
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Yildirim, Ali Önder
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Zeuschner, Dagmar
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Nicke, Annette
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Carlin, Leo M.
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Sperandio, Markus
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Stoeger, Tobias
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

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Rehberg, Markus
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

See full publications list
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Title:
The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation
Creators:
Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus
Identification Number:
10.1002/advs.202404661
Date:
4 December 2024
Divisions:
College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Publisher:
Wiley
Additional Information:
his work was supported by funding from the Deutsche Forschungsgemeinschaft (DFG, German Re-search Foundation) – Project-ID 335 447 717 – SFB 1328 (AN); by the German Federal Ministry of Education and Research (Infrafrontier grant01KX1012 to MHdA) and the German Center for Diabetes Research(DZD) (BR, MHdA); by a China Scholarship Council (CSC) fellowship(202 008 080 252) (CL); by funding from the European Union FET Proac-tive program (BOW – GA 952 183) (TS, MR) as well as the European Union under the HORIZON-CL4-2022-DIGITAL-EMERGING-01 program(NanoPass – GA101092741) (TS, MR).Open access funding enabled and organized by Projekt DEAL.
Library
URI:
https://pub.demo35.eprints-hosting.org/id/eprint/83
Item Type:
Article
Depositing User:
Unnamed user with email ejo1f20@soton.ac.uk
Date Deposited:
11 Jun 2025 16:34
Revision:
11
Last Modified:
12 Jun 2025 12:19
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