'Tissue' transglutaminase release from apoptotic cells into extracellular matrix during human liver fibrogenesis

Enhanced apoptosis characterizes several pathologies affecting human liver. This study sought to determine whether apoptosis is involved in the format ion of fibrotic lesions occurring in hepatic disease, The expression of Bcl -2 was analysed, and of 'tissue' transglutaminase (tTG), a cross-linking en zyme which recent evidence suggests plays a role in the formation of fibrot ic lesions in experimental settings, Regardless of the degree of liver inju ry, tTG abnormally accumulated in the liver cells adjacent to fibrotic tiss ue, Many cells showing DNA fragmentation and morphological features of apop tosis were also observed near fibrotic lesions, Bcl-2 was detected predomin antly in infiltrating lymphocytes within the liver tissue. Marked staining for both tTG protein and chromatin was also observed in the acellular fibro tic tissue, which suggested an active release of intracellular macromolecul es from the dying cells into the extracellular matrix, This study indicates that fibrogenesis in the liver is associated with the release of tTG from dying cells, By cross-linking extracellular matrix proteins, this enzyme mi ght play a role in the formation of fibrotic lesions, Copyright (C) 1999 Jo hn Wiley & Sons, Ltd.