Role of Kupffer cells in neutrophil activation and infiltration following total hepatic ischemia and reperfusion.

Abstract

This study was designed to examine the role of Kupffer cells in polymorphonuclear neutrophils (PMN) activation and infiltration after severe total hepatic ischemia. Male rats pretreated with either normal saline (NS group; n = 58) or gadolinium chloride (7 mg/kg; GC group, n = 57) for 2 days were subjected to 90 min total hepatic ischemia. In addition to 7-day survival rate, aspartate aminotransferase (AST), PMN liver infiltration, plasma myeloperoxidase (MPO), and interleukin-1 (IL-1) levels were serially measured from the end of ischemia to 360 min after reperfusion. Survival rate of the GC group significantly improved to 67% (P < 0.01), whereas that of the NS group remained at 20%. Extremely high AST levels (5,372 +/- 231 IU/liter) were obtained in the NS group, which correlated with the degree of hepatic necrosis. Very high IL-1 (270.3 +/- 91.2 pg/ml) and MPO (1.7 +/- 0.4 U/ml) levels were also seen in the NS group. The GC group significantly inhibited increases in AST, IL-1, and MPO levels as well as PMN infiltration in the liver compared to the NS group (P < 0.05). Our study demonstrated that Kupffer cell activation has an important role in the development of reperfusion injury after total hepatic ischemia through IL-1 release, and PMN activation and infiltration.