BACKGROUND/AIMS: In the transplanted liver, the role of apoptosis and apoptosis-related proteins are largely unknown. This study addresses the question whether hepatocyte or leukocyte apoptosis plays an important role in acute rejection of the transplanted @entity1 liver and which pathways are involved. METHODOLOGY: Cryosections from liver biopsies with acute rejection were stained with the TUNEL technique for detection of apoptosis and labeled immunohistochemically with antibodies against @entity1197 , @entity588 , @entity2533 and @entity3623 . A double-labeling protocol was developed for simultaneous detection of @entity3623 and apoptosis. Liver tissue with @entity3619 , with @entity99 reinfection and tissue without pathological findings served as a control. RESULTS: Leukocyte apoptosis was markedly reduced in severe compared to mild or moderate acute rejection. Hepatocyte apoptosis is detected rarely in acute rejection with a slight increase from mild to severe despite a strong expression of @entity1197 and @entity2533 on hepatocytes. The hepatocyte expression of @entity3623 is weak in acute rejection but strong in control slides with @entity1956 . In acute rejection, simultaneous expression of @entity3623 and apoptosis could be demonstrated in Kupffer-cells. CONCLUSIONS: Severe acute rejection in the @entity1 transplanted liver is characterized by a lack of apoptosis of infiltrating portal lymphocytes probably caused by a reduced downregulation of lymphocyte function. Secondly, in spite of the strong expression of @entity1197 and @entity7790 , hepatocyte apoptosis plays a limited role for @entity409 in acute rejection. Finally, Kupffer cell apoptosis is increased in acute rejection and seems to be induced by @entity842 .

Expression of apoptosis and apoptosis-related peptides in various stages of rejection in the XXXX transplanted liver.

@entity1 :: ('9606', 'Species') :: ['human'] @entity588 :: ('596', 'Gene') :: ['bcl-2'] @entity1956 :: ('MESH:D006509', 'Disease') :: ['hepatitis B/C reinfection'] @entity1197 :: ('355', 'Gene') :: ['CD95'] @entity7790 :: ('7039', 'Gene') :: ['TGF-alpha'] @entity409 :: ('MESH:D008107', 'Disease') :: ['liver damage'] @entity2533 :: ('7040', 'Gene') :: ['TGF-beta'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity3623 :: ('4843', 'Gene') :: ['iNOS'] @entity3619 :: ('MESH:D006521', 'Disease') :: ['chronic viral hepatitis'] @entity99 :: ('MESH:D056486', 'Disease') :: ['hepatitis']
@entity1 :: (9606,Species) :: ['human']
