Nanoparticle targeting of neutrophil glycolysis prevents lung ischemia-reperfusion injury
Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved..
Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G[2-DG]). Intravenously administered NP-Ly6G(2-DG) to mice exhibited high specificity for circulating neutrophils. NP-Ly6G(2-DG)-treated neutrophils were unable to adapt to hypoglycemic conditions of the lung airspace environment as evident by the loss of demand-induced glycolysis, reductions in glycogen and ATP content, and an increased vulnerability to apoptosis. NP-Ly6G(2-DG) treatment inhibited pulmonary IRI following hilar occlusion and orthotopic lung transplantation. IRI protection was associated with less airspace neutrophil extracellular trap generation, reduced intragraft neutrophilia, and enhanced alveolar macrophage efferocytotic clearance of neutrophils. Collectively, our data show that pharmacologically targeting glycolysis in neutrophils inhibits their activation and survival leading to reduced pulmonary IRI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons - (2024) vom: 24. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liao, Fuyi [VerfasserIn] |
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| Links: |
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| Themen: |
Acute lung injury and immunosuppression |
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| Anmerkungen: |
Date Revised 16.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.ajt.2024.03.028 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370123913 |
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| 520 | |a Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G[2-DG]). Intravenously administered NP-Ly6G(2-DG) to mice exhibited high specificity for circulating neutrophils. NP-Ly6G(2-DG)-treated neutrophils were unable to adapt to hypoglycemic conditions of the lung airspace environment as evident by the loss of demand-induced glycolysis, reductions in glycogen and ATP content, and an increased vulnerability to apoptosis. NP-Ly6G(2-DG) treatment inhibited pulmonary IRI following hilar occlusion and orthotopic lung transplantation. IRI protection was associated with less airspace neutrophil extracellular trap generation, reduced intragraft neutrophilia, and enhanced alveolar macrophage efferocytotic clearance of neutrophils. Collectively, our data show that pharmacologically targeting glycolysis in neutrophils inhibits their activation and survival leading to reduced pulmonary IRI | ||
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| 650 | 4 | |a efferocytosis | |
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| 650 | 4 | |a ischemia-reperfusion injury | |
| 650 | 4 | |a lung transplant | |
| 650 | 4 | |a nanoparticles | |
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| 700 | 1 | |a Scozzi, Davide |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Dequan |e verfasserin |4 aut | |
| 700 | 1 | |a Maksimos, Mina |e verfasserin |4 aut | |
| 700 | 1 | |a Diedrich, Camila |e verfasserin |4 aut | |
| 700 | 1 | |a Cano, Marlene |e verfasserin |4 aut | |
| 700 | 1 | |a Tague, Laneshia K |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhyi |e verfasserin |4 aut | |
| 700 | 1 | |a Haspel, Jeffrey A |e verfasserin |4 aut | |
| 700 | 1 | |a Leonard, Jennifer M |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Krupnick, Alexander S |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Brian W |e verfasserin |4 aut | |
| 700 | 1 | |a Kreisel, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Azab, Abdel Kareem |e verfasserin |4 aut | |
| 700 | 1 | |a Gelman, Andrew E |e verfasserin |4 aut | |
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