Transcriptional activation of vascular cell adhesion molecule-1 gene in vivo and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock.

摘要: Polymorphonuclear leukocytes (neutrophils) can cause hepatic parenchymal cell injury during endotoxin (ET) shock. Because adhesion molecules are critical for inflammatory damage, the role of vascular molecule-1 (VCAM-1) was studied in pathophysiology ET ET-sensitive mice (C3Heb/FeJ) were treated with 700 mg/kg galactosamine combination 100 microg/kg Salmonella abortus equi ET, 15 TNF-alpha, or 13 to 23 IL-1. VCAM-1 mRNA formation strongly activated animals In contrast, only TNF-alpha and IL-1, not induced gene transcription livers ET-resistant (C3H/HeJ). Immunohistochemistry isolation liver cells endotoxemia indicated that protein formed endothelial Kupffer cells, hepatocytes. Galactosamine/ET neutrophil accumulation sinusoids (515 +/- 30 neutrophils/50 high power fields) followed by transmigration at 7 h. At time, severe observed (necrosis, 53 5%). An anti-VCAM-1 Ab (3 mg/kg) attenuated area necrosis 60%. The reduced 84%, but had no effect on total number vasculature. Flow cytometric analysis identified presence very late Ag-4 mouse peripheral neutrophils. Our data demonstrated cytokine-dependent expression endotoxemia. Neutrophils able use Ag-4/VCAM-1 interactions transmigrate into parenchyma vivo. Preventing blocking protected hepatocytes against neutrophil-induced injury.