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Published on: November 10, 2023
Apoptosis in acute pulmonary allograft rejection and cytomegalovirus infection
P R Hansen1, A M Holm, U G Svendsen
1The Heart Center, Rigshospitalet, Copenhagen, Denmark.
Abstract:
Apoptosis is a form of programmed cell death, characterized by activation of endonucleases that cleave DNA into oligonucleosomal fragments, which can be identified by in situ terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL). This process has recently been implicated in cardiac and hepatic allograft rejection, and we investigated its contribution to acute pulmonary allograft rejection and cytomegalovirus (CMV) pneumonitis by in situ TUNEL of transbronchial biopsy specimens. In situ TUNEL was performed on 70 transbronchial biopsy samples collected from 25 pulmonary allograft recipients for diagnosis of acute rejection or CMV pneumonitis, and the number of apoptotic nuclei/mm2 was correlated with the rejection grade (International Society of Heart and Lung Transplantation classification). During acute pulmonary allograft rejection, apoptotic nuclei were demonstrated in pulmonary parenchymal cells and mononuclear infiltrating cells, and the number of apoptotic cells was positively correlated with the rejection grade. In addition, a marked increase in the density of apoptotic cells was found in pulmonary allografts with CMV pneumonitis. We conclude that apoptosis contributes to cell death during acute pulmonary allograft rejection and CMV infection.
Insights
Apoptosis, programmed cell death, is increased in acute pulmonary allograft rejection and cytomegalovirus (CMV) pneumonitis. This finding suggests apoptosis plays a key role in lung transplant complications.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Apoptosis, or programmed cell death, involves DNA fragmentation identifiable by in situ terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL).
- Apoptosis has been linked to cardiac and hepatic allograft rejection.
Purpose of the Study:
- To investigate the role of apoptosis in acute pulmonary allograft rejection.
- To determine the contribution of apoptosis to cytomegalovirus (CMV) pneumonitis in lung transplant recipients.
Main Methods:
- In situ TUNEL staining was performed on 70 transbronchial biopsy specimens from 25 pulmonary allograft recipients.
- The density of apoptotic nuclei was quantified and correlated with rejection grade (ISHLT classification) and CMV infection.
Main Results:
- Apoptotic cells were found in pulmonary parenchymal and infiltrating mononuclear cells during acute rejection.
- A positive correlation existed between apoptotic cell numbers and the severity of acute pulmonary allograft rejection.
- Elevated apoptotic cell density was observed in pulmonary allografts with CMV pneumonitis.
Conclusions:
- Apoptosis significantly contributes to cell death in acute pulmonary allograft rejection.
- Apoptosis is implicated in the pathogenesis of CMV pneumonitis following lung transplantation.
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