BACKGROUND: Acute pancreatitis remains a disease of uncertain pathogenesis. The resolution of the cellular events that underlie the development of pancreatitis may allow for significant advances in therapy. METHODS: A new experimental approach to acute pancreatitis in the rat, i.e., selective ligation of pancreatic ducts and immunohistochemical analysis of cellular kinetics using a panel of monoclonal antibodies, was devised. RESULTS: Immunostaining showed that the majority of the infiltrating cells bore macrophage-specific antigens (ED1-positive). Some neutrophils were also among the cellular infiltrate, but only a few T (OX19-positive) or B (His14-positive) lymphocytes were seen. At a later stage, more than half of the mononuclear cells in the stroma were neither macrophages nor lymphocytes, but possibly fibroblasts. In vivo labeling of proliferating cells with 5-bromo-2'-deoxyuridine and immunostaining showed active proliferation of duct epithelial and wall cells of the interlobular pancreatic duct on days 1 and 2, proliferation of nonacinar cells on days 1-4, and proliferation of acinar cells on days 2-28. CONCLUSIONS: These results indicate an important role of macrophages and the presence of complex processes of degeneration and regeneration in duct ligation-induced pancreatitis.
BACKGROUND:Acute pancreatitis remains a disease of uncertain pathogenesis. The resolution of the cellular events that underlie the development of pancreatitis may allow for significant advances in therapy. METHODS: A new experimental approach to acute pancreatitis in the rat, i.e., selective ligation of pancreatic ducts and immunohistochemical analysis of cellular kinetics using a panel of monoclonal antibodies, was devised. RESULTS: Immunostaining showed that the majority of the infiltrating cells bore macrophage-specific antigens (ED1-positive). Some neutrophils were also among the cellular infiltrate, but only a few T (OX19-positive) or B (His14-positive) lymphocytes were seen. At a later stage, more than half of the mononuclear cells in the stroma were neither macrophages nor lymphocytes, but possibly fibroblasts. In vivo labeling of proliferating cells with 5-bromo-2'-deoxyuridine and immunostaining showed active proliferation of duct epithelial and wall cells of the interlobular pancreatic duct on days 1 and 2, proliferation of nonacinar cells on days 1-4, and proliferation of acinar cells on days 2-28. CONCLUSIONS: These results indicate an important role of macrophages and the presence of complex processes of degeneration and regeneration in duct ligation-induced pancreatitis.