TRANSFORMING GROWTH-FACTOR BETA(1), EXTRACELLULAR-MATRIX, AND INFLAMMATORY CELLS IN WOUND REPAIR USING A CLOSED DUODENAL LOOP PANCREATITIS MODEL RAT - IMMUNOHISTOCHEMICAL STUDY

Background: Serial changes in the localization of various components of extracellular matrix in acute pancreatitis have been reported, but there have been no reports on serial changes in the localization of transforming growth factor beta and the determination of cells producing extracellular matrix. Methods: In this study serial relationships between the localization of transforming growth factor beta(1), fibronectin and type-III collagen, inflammatory cells, and serum amylase levels in the process of tissue repair in acute pancreatitis were studied using a closed duodenal loop model rat. Furthermore, the cells producing transforming growth factor beta(1), fibronectin, and type-III collagen were investigated by immunoelectron microscopy. Results: Three to 6 h after duodenal ligation slight localization of transforming growth factor beta(1) and fibronectin and inflammatory cell infiltration were observed in the interlobular space. Twelve to 24 h after duodenal ligation the infiltration of polymorphonuclear leukocytes and the deposition of transforming growth factor beta(1) and fibronectin were observed extensively in the interlobular and intralobular spaces. After release of the loop, infiltration of fibroblasts and marked deposition of fibronectin and type-III collagen were observed around the tubular complexes, but the deposition of transforming growth factor beta(1) was slight. Also, fibronectin and type-III collagen were shown to be produced by fibroblasts and acinar cells. Conclusions: These findings suggest that transforming growth factor beta(1) appears at the injured sites from the early stage of acute pancreatitis. Moreover, it is extensively related to the production of extracellular matrix such as fibronectin and type-III collagen. Furthermore, these substances are closely involved in the healing process of acute pancreatitis.