Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation.
OBJECTIVE
To examine the presence and extent of apoptosis as well as the affected cell types in human lung tissue before, during, and after transplantation.


BACKGROUND
Apoptosis has been described in various human and animal models of ischemia-reperfusion injury, including heart, liver, and kidney, but not in lungs. Therefore, the presence of apoptosis and its role in human lungs after transplantation is not clear.


METHODS
Lung tissue biopsies were obtained from 20 consecutive human lungs for transplantation after cold ischemic preservation (1-5 hours), after warm ischemia time (during implantation), and 30, 60, and 120 minutes after graft reperfusion. To detect and quantify apoptosis, fluorescent in situ end labeling of DNA fragments (TUNEL assay) was used. Electron microscopy was performed to verify the morphologic changes consistent with apoptosis and to identify the cell types, which were lost by apoptosis.


RESULTS
Almost no evidence of apoptosis was found in specimens after immediate cold and warm ischemic periods. Significant increases in the numbers of cells undergoing apoptosis were observed after graft reperfusion in a time-dependent manner. The mean fraction of apoptotic cells at 30, 60, and 120 minutes after graft reperfusion were 16.6%, 22.1%, and 34.9% of total cells, respectively. Most of the apoptotic cells appeared to be alveolar type II pneumocytes, as confirmed by electron microscopy.


CONCLUSIONS
Programmed cell death (apoptosis) appears to be a significant type of cell loss in human lungs after transplantation, and this may contribute to ischemia-reperfusion injury during the early phase of graft reperfusion. This cell loss might be responsible for severe organ dysfunction, which is seen in 20% of patients after lung transplantation. Therefore, this work is of importance to surgeons for the future development of interventions to prevent cell death in transplantation.
Fischer
S
S
Division of Thoracic Surgery, Toronto General Hospital, Ontario, Canada.
Cassivi
S D
SD
Xavier
A M
AM
Cardella
J A
JA
Cutz
E
E
Edwards
V
V
Liu
M
M
Keshavjee
S
S
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D017209:Apoptosis; D001706:Biopsy; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000473:pathology*; D008168:Lung / Q000098:blood supply* / Q000473:pathology*; D016040:Lung Transplantation / Q000473:pathology* / Q000706:statistics & numerical data; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D013997:Time Factors