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 organ failure remain unknown. To clarify the role of endothelial activation, we examined the effects of ascitic fluids from rats with experimental pancreatitis on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). Necrotizing hemorrhagic pancreatitis was induced with sodium taurocholate. Six and 24 h later, peritoneal exudates were collected, centrifuged and HUVECs were treated with the supernatants. The expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was quantified by enzyme-linked immunosorbent assay. Induction of mRNA was assessed by reverse-transcriptase polymerase chain reaction. The activation of transcription factors was examined by electrophoretic mobility shift assay. The expression of ICAM-1 in the tissues was examined immunohistochemically. ICAM-1 and VCAM-1, but not E-selectin expression was upregulated with comparable mRNA induction. Nuclear factor kappaB was activated, while activator protein-1 binding activity was not altered. 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 adhesion molecules, and ICAM-1 may play roles in the pathogenesis of complicated AP.
Masamune
A
A
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Shimosegawa
T
T
Kimura
K
K
Fujita
M
M
Sato
A
A
Koizumi
M
M
Toyota
T
T
D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006358:Hot Temperature; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism*; D011489:Protein Denaturation / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1