Sustained apoptosis in human cardiac allografts despite histologic resolution of rejection.
BACKGROUND
We investigated the occurrence of apoptosis during and after resolution of cardiac allograft rejection. Apoptosis could play different roles in graft survival depending on the target cells; thus, we also determined the cell types involved.


METHODS
Endomyocardial biopsy specimens were evaluated during the first 6 months after transplantation as follows: group I, no current or prior rejection; group II, during an episode of moderate rejection; and group III, histologic resolution after an episode of moderate rejection.


RESULTS
Groups II and III showed significantly increased apoptotic activity, indicated by increased caspase-8 and caspase-3 activity; however, activated caspase-3 was undetectable in group I. Activated caspase-3 was detected only in groups II and III. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling was detected in groups II and III but not group I and predominantly in inflammatory cells.


CONCLUSIONS
Increased caspase activity and apoptosis of infiltrating cells not only occurs during acute cardiac allograft rejection but persists after histologic resolution. Thus, programmed cell death occurs beyond the period of histologic resolution and may play a role in regulation of the rejection process.
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology*; D016027:Heart Transplantation; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D014184:Transplantation, Homologous
D004792:Enzyme Precursors; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases