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 cel l types in human lung tissue before, during, and after transplantation. Summary Background Data 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 tran splantation is not clear. Methods Lung tissue biopsies were obtained from 20 consecutive human lungs for tran splantation after cold ischemic preservation (1-5 hours), after warm ischem ia time (during implantation), and 30, 60, and 120 minutes after graft repe rfusion. 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 identif y 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 u ndergoing apoptosis were observed after graft reperfusion in a time-depende nt 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, respec tively. Most of the apoptotic cells appeared to be alveolar type II pneumoc ytes, 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 ische mia-reperfusion injury during the early phase of graft reperfusion. This ce ll loss might be responsible for severe organ dysfunction, which is seen in 20% of patients after lung transplantation. Therefore, this work is of imp ortance to surgeons for the future development of interventions to prevent cell death in transplantation.