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Status |
Public on Mar 30, 2022 |
Title |
Macrophage infiltration induced by donor hypovolemia protects against severe primary graft dysfunction in mouse lung transplantation |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
BACKGROUND: Hypovolemia is common in lung donors before or after brain death. However, its impact on primary graft function (PGD) remains obscure. METHODS: A clinically relevant two-hit model of PGD was established by integrating hypovolemic shock (HS) and cold ischemia-reperfusion in a mouse model of orthotopic lung transplantation (LTx) from C57BL/6 to Balb/c. At -48 hours, HS was induced to donor by withdrawal of blood from femoral artery and keeping the mean arterial pressure at 15±5 mmHg for 4 h. At -24 hours, donor lungs were retrieved from mice with or without HS and stored at 0ºC until transplantation. CD11b-DTR mice were used as donor and treated with Diphtheria Toxin (DT) to deplete graft-infiltrating macrophages. RESULTS: HS mainly caused macrophage-predominant infiltration around pulmonary artery injury systemic inflammatory response, but little impairment of lung function even if in combination with cold ischemia-reperfusion. Transcriptional profiling showed HS pretreatment increased pulmonary damage and alveolar remodeling but ameliorated inflammatory infiltration when compared to one-hit model of 12 hours cold ischemia-reperfusion injury. The allografts with donor DT-treatment one day ahead of HS showed injury and dysfunction at donation and worsened further at 24 hours reperfusion, whereas the allografts with recipient DT-treatment immediately after transplantation showed similar function and histology to the control treated with saline. CONCLUSION: Donor hypovolemia causes pulmonary artery injury and infiltration but has little impact on allograft function, even in combination with 24 h cold ischemia. Graft-infiltrating macrophages are critical in protecting graft from HS-induced injury and cold ischemia-reperfusion injury.
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Overall design |
Transcriptional profiling were performed on three naïve lung samples, three lung allografts that experienced 24 hours of cold ischemia and 2 hours of reperfusion, and three lung allografts that experienced additionally 4 hours of hypovolemic shock and 20 hours recovery before ischemia-reperfusion.
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Contributor(s) |
Wang X |
Citation missing |
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Submission date |
Aug 17, 2020 |
Last update date |
Mar 30, 2022 |
Contact name |
XINGAN WANG |
E-mail(s) |
tomorrow8621@gmail.com
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Phone |
3142299129
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Organization name |
University of Pittsburgh
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Department |
Medicine
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Lab |
Lung transplantation
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Street address |
200 Lothrop Street, W1206A
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City |
Pittsburgh |
State/province |
Pennsylvania (PA) |
ZIP/Postal code |
15261 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (9)
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Relations |
BioProject |
PRJNA657514 |
SRA |
SRP277778 |