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Updated: Jan 31, 2026
08:22
Orthotopic Left Lung Transplantation in Rats
Published on: July 3, 2025
741
Mitochondrial damage-associated molecular patterns released by lung transplants are associated with primary graft
Davide Scozzi1,2, Mohsen Ibrahim1,3, Fuyi Liao1
1Department of Surgery, Washington University School, St. Louis, Missouri.
Summary
High levels of mitochondrial DNA (mtDNA) correlate with severe primary graft dysfunction (PGD) after lung transplants. Inhibiting formylated peptide receptor 1 (FPR1) reduces lung graft injury by controlling neutrophil responses to damaged mitochondria.
Area of Science:
- Immunology
- Transplantation Biology
- Mitochondrial Medicine
Background:
- Primary graft dysfunction (PGD) significantly impacts lung transplant outcomes.
- Mitochondrial damage-associated molecular patterns (mtDAMPs) are implicated in organ injury, but their role in PGD is not fully understood.
Purpose of the Study:
- To investigate the association between circulating mitochondrial DNA (mtDNA) and PGD severity.
- To elucidate the role of formylated peptide receptor 1 (FPR1) in PGD pathogenesis and neutrophil-mediated graft injury.
Main Methods:
- Quantification of plasma mtDNA in lung transplant recipients before and after surgery.
- Establishment of a mouse orthotopic lung transplant model to study PGD.
- Pharmacologic inhibition and genetic deletion of FPR1 in the mouse model.
- Analysis of neutrophil trafficking and mitochondrial engulfment within lung grafts.
Main Results:
- Elevated circulating mtDNA levels were associated with severe PGD.
- Inhibition or genetic deletion of FPR1 significantly reduced lung graft injury in mice.
- FPR1 mediates neutrophil migration and retention in airways, coupled with damaged mitochondria engulfment.
- Engulfment of damaged mitochondria by neutrophils triggers ROS production and pulmonary edema.
Conclusions:
- mtDAMPs, specifically mtDNA, are linked to PGD development.
- FPR1 signaling is a critical pathway driving neutrophil-mediated lung graft damage.
- Targeting FPR1 may offer a therapeutic strategy to mitigate PGD after lung transplantation.
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