Specific induction of adhesion molecules in human vascular endothelial cells by rat experimental pancreatitis-associated ascitic fluids

The molecular mechanisms that link acute pancreatitis (AP) and multiple org an failure remain unknown. To clarify the role of endothelial activation, w e examined the effects of ascitic fluids from rats with experimental pancre atitis on the expression of adhesion molecules in human umbilical vein endo thelial cells (HUVECs). Necrotizing hemorrhagic pancreatitis was induced wi th sodium taurocholate. Six and 24 h later, peritoneal exudates were collec ted, centrifuged and HUVECs were treated with the supernatants. The express ion of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was quantified by enzyme-linked immunosor bent assay. Induction of mRNA was assessed by reverse-transcriptase polymer ase chain reaction. The activation of transcription factors was examined by electrophoretic mobility shift assay. The expression of ICAM-1 in the tiss ues was examined immunohistochemically. ICAM-1 and VCAM-1, but not E-select in expression was upregulated with comparable mRNA induction. Nuclear facto r KB was activated, while activator protein-1 binding activity was not alte red. Immunohistochemically, enhanced ICAM-1 expression was observed in the pancreas and lung, but not in the liver. Ascitic fluids may contain soluble factors responsible for the transcriptional activation of endothelial adhe sion molecules, and ICAM-1 may play roles in the pathogenesis of complicate d AP.