Apoptosis is a form of programmed cell death, characterized by activation o
f 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 i
n cardiac and hepatic allograft rejection, and we investigated its contribu
tion to acute pulmonary allograft rejection and cytomegalovirus (CMV) pneum
onitis by in situ TUNEL of transbronchial biopsy specimens. In situ TUNEL w
as performed on 70 transbronchial biopsy samples collected from 25 pulmonar
y allograft recipients for diagnosis of acute rejection or CMV pneumonitis,
and the number of apoptotic nuclei/mm(2) was correlated with the rejection
grade (International Society of Heart and Lung Transplantation classificat
ion). During acute pulmonary allograft rejection, apoptotic nuclei were dem
onstrated in pulmonary parenchymal cells and mononuclear infiltrating cells
, and the number of apoptotic cells was positively correlated with the reje
ction grade. In addition, a marked increase in the density of apoptotic cel
ls was found in pulmonary allografts with CMV pneumonitis. We conclude that
apoptosis contributes to cell death during acute pulmonary allograft rejec
tion and CMV infection.