APOPTOSIS AS A MECHANISM OF CELL-DEATH IN LIVER ALLOGRAFT-REJECTION

It is generally recognized that there are two mechanisms of cell death , apoptosis and necrosis, Apoptosis-programmed cell death-is involved in numerous states of physiological cell deletion, Recent studies have demonstrated that hepatocytes, under certain conditions, undergo apop tosis, The purpose of this work was to determine if apoptotic cell dea th is involved in liver allograft rejection, Groups of Lewis (RT1(l)) rats underwent orthotopic liver transplantation (OLT) from disparate D A (RT1(a)) or syngeneic Lewis rats, Liver samples were harvested at 1, 2, 3, 4, and 7 days posttransplant and analyzed for apoptotic cell de ath, Since the characteristics of apoptosis are difficult to discern u sing routine hematoxylin and eosin staining, we utilized a novel metho d that detects the classic indicator of apoptosis, nonrandom DNA degra dation. Paraffin-embedded tissue sections were end-labeled with nonrad ioactive dUTP and detection of apoptotic bodies accomplished by immuno assay. The incidence of apoptotic cells increased steadily over time i n allografts, in contrast to syngeneic grafts, In this study apoptotic cell death paralleled standard indicators of liver allograft rejectio n including pathology, mononuclear cell infiltration, and increases in liver enzymes, Moreover, increased expression of TGF-beta 1 correlate d with apoptosis in liver allografts, supporting the previously descri bed role for this cytokine in hepatocyte apoptosis, Our results demons trate, for the first time, that apoptosis may be a mechanism of cell d eath in liver allograft rejection