CHEMOKINE INVOLVEMENT IN HEPATIC ISCHEMIA REPERFUSION INJURY IN MICE - ROLES FOR MACROPHAGE INFLAMMATORY PROTEIN-2 AND KC (VOL 27, PG 507, 1998)/

Hepatic injury induced by ischemia and reperfusion is an important cli nical problem after liver resection or transplantation. Neutrophils ar e known to mediate the organ injury, but the precise mechanisms leadin g to hepatic neutrophil recruitment are undefined. Two CSC chemokines, macrophage inflammatory protein-2 (MIP-2) and KC, are potently chemot actic for neutrophils in vitro and have been reported to be involved i n neutrophil-dependent inflammatory tissue injury. The objective of th e present study was to determine the roles of MIP-2 and KC in the indu ction of hepatic ischemia/reperfusion injury. C57BL/6 mice were subjec ted to 90 minutes of partial hepatic ischemia followed by reperfusion. Hepatic injury was associated with neutrophil sequestration, edema, a nd elevated serum levels of hepatic transaminases. The expression of M IP-2 messenger RNA (mRNA) was induced within 3 hours after reperfusion , before any detectable increase in neutrophil accumulation, and was a lso increased to a greater extent in the ischemic lobe after 9 hours o f reperfusion. These data suggest that MIP-2 may be involved in the in itial recruitment of neutrophils to the ischemic lobe. In contrast, KC mRNA expression was not increased after 3 hours of reperfusion but af ter 9 hours increased equivalently in both ischemic and nonischemic lo bes, suggesting a more generalized role in neutrophil recruitment. Neu tralization of MIP-2 or KC resulted in significant decreases in hepati c neutrophil accumulation, edema, and hepatocellular injury. These dat a suggest that the local expression of MIP-2 and KC are important medi ators involved in neutrophil-dependent hepatic injury induced by ische mia and reperfusion in mice.