Differential local and systemic regulation of the murine chemokines KC andMIP2

We characterized the relative biological activity and expression of two mur ine chemokines that may serve as functional homologues for human IL-8, KC, and macrophage inflammatory protein 2 (MIP2). Recombinant chemokines were p roduced in bacterial expression systems and antibodies specific for KC or M IP2 were raised. In vitro assays showed that KC elicited 4-fold greater neu trophil chemotaxis compared with MIP2, while MIP2 elicited significantly gr eater release of elastase. Lipopolysaccharide- (LPS) stimulated macrophages (8 h) secreted more MIP2 (approximately 10 ng/mL) compared with KC (approx imately 4 ng/ml) and expression of either murine chemokine was independent of TNF alpha or IL-1 beta production. Thioglycollate (thio) and glycogen (g ly) induced peritonitis produced more KC (thio = 7.1 and gly = 2.5 ng/mL) i n the peritoneum compared with MIP2 (thio = 4.5 and gly = 0.3 ng/mL). Plasm a KC levels were very high after either challenge (similar to 24 ng/mL), wh ich was >50-fold more than the systemic increase in MIP2 (similar to0.3 ng/ mL). Our data demonstrate that while KC and MIP2 have similar in vitro prod uction characteristics, KC appears to be a more potent and systemically dis tributed chemokine during acute in vivo inflammation, while MIP2 expression appears limited to localized expression.