Apoptosis of mononuclear cell infiltrates in cardiac allograft biopsy specimens questions studies of biopsy-cultured cells
Abstract
During acute rejection, CD4 and CD8 T cells infiltrate the myocardium and cause myocyte death and dropout. CD4 and CD8 cells use a number of cytotoxic mechanisms, including fas-fas ligand interactions, which lead to apoptotic death. Since fas is expressed on myocytes, we investigated endomyocardial biopsy specimens from cardiac transplant patients to determine whether apoptosis is one of the mechanisms of cell death in acute rejection. Serial sections of individual endomyocardial biopsy specimens from patients histologically diagnosed as having grade 3A rejection (n=22 biopsy specimens), biopsy specimens showing a typical "Quilty effect" (n=10), and specimens with concurrent grade 3A rejection and the Quilty effect (n=6) were evaluated using the C-terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique for frequency of apoptosis in myocytes and mononuclear cell infiltrates. None of the examined sections showed detectable evidence of apoptotic myocytes, even within regions clearly showing myocyte damage. Of interest was our consistent finding that 85-98% of mononuclear cell infiltrates within biopsy specimens scored as having grade 3A rejection had undergone apoptosis. In marked contrast, 9...Continue Reading
References
Citations
Expression of Fas, FasL, and soluble Fas mRNA in endomyocardial biopsies of human cardiac allografts
In vivo imaging of acute cardiac rejection in human patients using (99m)technetium labeled annexin V
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis