LONG-TERM IMPAIRED NEUTROPHIL MIGRATION IN MICE OVEREXPRESSING HUMAN INTERLEUKIN-8

The proinflammatory chemokine interleukin-8 (IL-8/NAP-1) has been impl icated in recruiting neutrophils to sites of acute and chronic tissue inflammation. In transgenic mice, elevated serum IL-8 levels ranging f rom 1 to 118 ng/ml were correlated with proportional increases in circ ulating neutrophils and proportional decreases in L-selectin expressio n on the surface of blood neutrophils. No change in the expression of the beta 2-integrins Mac-1 and LFA-1 was apparent on peripheral blood neutrophils of the IL-8 transgenic mice. Additionally, L-selectin expr ession on bone marrow neutrophils and neutrophil precursors was normal in all transgenic lines. IL-8 transgenic mice demonstrated an accumul ation of neutrophils in the microcirculation of the lung, liver and sp leen. Moreover, there was no evidence of neutrophil extravasation, pla sma exudation or tissue damage in any IL-8 transgenic mice. Neutrophil migration into the inflamed peritoneal cavity was severely inhibited in IL-8 transgenic mice, but not in nontransgenic littermates. The IL- 8 transgenic mice should serve as useful models for studying the putat ive role of neutrophils in mediating tissue damage in models of inflam mation, such as hepatic ischemia and reperfusion injury, cecal punctur e and ligation, and glomerulonephritis.