Resolvin D1 prevents injurious neutrophil swarming in transplanted lungs
Neutrophils are the primary cell type involved in lung ischemia-reperfusion injury (IRI), which remains a frequent and morbid complication after organ transplantation. Endogenous lipid mediators that become activated during acute inflammation-resolution have gained increasing recognition for their protective role(s) in promoting the restoration of homeostasis, but their influence on early immune responses following transplantation remains to be uncovered. Resolvin D1, 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid (RvD1), is a potent stereoselective mediator that exhibits proresolving and anti-inflammatory actions in the setting of tissue injury. Here, using metabololipidomics, we demonstrate that endogenous proresolving mediators including RvD1 are increased in human and murine lung grafts immediately following transplantation. In mouse grafts, we observe lipid mediator class switching early after reperfusion. We use intravital two-photon microscopy to reveal that RvD1 treatment significantly limits early neutrophil infiltration and swarming, thereby ameliorating early graft dysfunction in transplanted syngeneic lungs subjected to severe IRI. Through integrated analysis of single-cell RNA sequencing data of donor and recipient immune cells from lung grafts, we identify transcriptomic changes induced by RvD1. These results support a role for RvD1 as a potent modality for preventing early neutrophil-mediated tissue damage after lung IRI that may be therapeutic in the clinics.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 120(2023), 31 vom: 15. Aug., Seite e2302938120 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Wenjun [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.07.2023 Date Revised 25.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2302938120 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM359873103 |
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| 245 | 1 | 0 | |a Resolvin D1 prevents injurious neutrophil swarming in transplanted lungs |
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| 520 | |a Neutrophils are the primary cell type involved in lung ischemia-reperfusion injury (IRI), which remains a frequent and morbid complication after organ transplantation. Endogenous lipid mediators that become activated during acute inflammation-resolution have gained increasing recognition for their protective role(s) in promoting the restoration of homeostasis, but their influence on early immune responses following transplantation remains to be uncovered. Resolvin D1, 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid (RvD1), is a potent stereoselective mediator that exhibits proresolving and anti-inflammatory actions in the setting of tissue injury. Here, using metabololipidomics, we demonstrate that endogenous proresolving mediators including RvD1 are increased in human and murine lung grafts immediately following transplantation. In mouse grafts, we observe lipid mediator class switching early after reperfusion. We use intravital two-photon microscopy to reveal that RvD1 treatment significantly limits early neutrophil infiltration and swarming, thereby ameliorating early graft dysfunction in transplanted syngeneic lungs subjected to severe IRI. Through integrated analysis of single-cell RNA sequencing data of donor and recipient immune cells from lung grafts, we identify transcriptomic changes induced by RvD1. These results support a role for RvD1 as a potent modality for preventing early neutrophil-mediated tissue damage after lung IRI that may be therapeutic in the clinics | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a inflammation | |
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| 700 | 1 | |a Shepherd, Hailey M |e verfasserin |4 aut | |
| 700 | 1 | |a Terada, Yuriko |e verfasserin |4 aut | |
| 700 | 1 | |a Shay, Ashley E |e verfasserin |4 aut | |
| 700 | 1 | |a Bery, Amit I |e verfasserin |4 aut | |
| 700 | 1 | |a Gelman, Andrew E |e verfasserin |4 aut | |
| 700 | 1 | |a Lavine, Kory J |e verfasserin |4 aut | |
| 700 | 1 | |a Serhan, Charles N |e verfasserin |4 aut | |
| 700 | 1 | |a Kreisel, Daniel |e verfasserin |4 aut | |
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