NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE156322 Query DataSets for GSE156322
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
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.
 
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.
 
Contributor(s) Wang X
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Aug 17, 2020
Last update date Mar 30, 2022
Contact name XINGAN WANG
E-mail(s) tomorrow8621@gmail.com
Phone 3142299129
Organization name University of Pittsburgh
Department Medicine
Lab Lung transplantation
Street address 200 Lothrop Street, W1206A
City Pittsburgh
State/province Pennsylvania (PA)
ZIP/Postal code 15261
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (9)
GSM4729074 XW745L: 24h CI/2h Reperfusion rep1
GSM4729075 XW749L: 24h CI/2h Reperfusion rep2
GSM4729076 XW755L: 24h CI/2h Reperfusion rep3
Relations
BioProject PRJNA657514
SRA SRP277778

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE156322_Processed-mouse_lung_transplant-CI2RvsNaive_DEG.txt.gz 3.0 Mb (ftp)(http) TXT
GSE156322_Processed-mouse_lung_transplant-HSCI2RvsCI2R_DEG.txt.gz 2.9 Mb (ftp)(http) TXT
GSE156322_Processed-mouse_lung_transplant-HSCI2RvsNaive_DEG.txt.gz 3.0 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.