APOPTOTIC TUBULAR CELL-DEATH DURING ACUTE RENAL-ALLOGRAFT REJECTION

Tubular cells are important targets during acute renal allograft rejec tion and induction of apoptosis might be a mechanism of tubular cell d estruction. Susceptibility to induction of apoptosis is regulated bq t he homologous Bcl-2 and Bax proteins, Expression of Bcl-2 and Bar is r egulated by p53, which down-regulates expression of Bcl-2, while simul taneously up-regulating expression of Bax. We studied apoptotic tubula r cell death in 10 renal allograft biopsies from transplant recipients with acute rejection by in situ end-labelling and the DNA-binding flu orochrome propidium iodide. Tubular expression of p53, Bcl-2 and Bax w as studies by immunohistochemistry. Five renal allograft biopsies from transplant recipients with uncomplicated clinical course and histolog ically normal renal tissue present in nephrectomy specimens from 4 pat ients with renal adenocarcinoma served as control specimens. Apoptotic cells and apoptotic bodies were detected in tubular epithelia and tub ular lumina in 9 out of 10 acute rejection biopsies. In control renal tissue, apoptotic cells were detected in 1 biopsy only. Compared to co ntrol renal tissue, acute renal allograft rejection was, furthermore, associated with a shift in the ratio of Bcl-2 to Bax in favour of Bax in tubular epithelia and increased expression of p53 in tubular nuclei . These observations demonstrate that apoptosis contributes in part to tubular cell destruction during acute renal allograft rejection. In a ccordance, the shift in the ratio of Bcl-2 to Bax in favour of Bax ind icates increased susceptibility of tubular epithelia to induction of a poptosis. The expression of p53 in tubular nuclei during acute renal a llograft rejection indicates the presence of damaged DNA, which can be important in initiation of part of the observed apoptosis, These find ings elucidate part of the mechanisms controlling apoptotic tubular ce ll death during acute renal allograft rejection.