Apoptosis in acute pulmonary allograft rejection and cytomegalovirus infection

PETER RIIS HANSEN,' ANNE METTE HOLM,' ULRIK GERNER SVENDSEN,' PETER SKOV OLSEN' and CLAUS B0GELUND ANDERSEN' 'The Heart Center, and 2Department of Pathology, Rigshospitalet, Copenhagen, Denmark Hansen PR, Holm AM, Svendsen UG, Olsen PS & Andersen CB. Apoptosis in acute pulmonary allograft rejection and cytomegalovirus infection. APMIS 1999;107:529-34. 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 deoxyribon- ucleotide 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 trans- bronchial 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 nucleilmm' was correlated with the rejection grade (International Society of Heart and Lung Transplantation classification). During acute pulmonary allograft rejection, apop- totic 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 pneu- monitis. We conclude that apoptosis contributes to cell death during acute pulmonary allograft rejec- tion and CMV infection. Key words: Apoptosis; lung allograft rejection; cytomegalovirus pneumonitis. Peter Riis Hansen, Department of Cardiology