Macrophage inflammatory protein-2 induced by TNF-alpha plays a pivotal role in concanavalin A-induced liver injury in mice.

Elsevier , Nakamura, K; Okada, M; Yoneda, M; Takamoto, S; Nakade, Y; Tamori, K; Aso, K; Makino, I, JOURNAL OF HEPATOLOGY, 35(2), 2001, 217-224. authorBackground/Aims: Macrophage inflammatory protein-2 (MIP-2), one of CXC chemokines is involved in the recruitment of neutrophils in several tissue injury. In this study, we investigated a role of MIP-2 in concanavalin A (Con A)-induced liver injury in mice. Methods:Liver injury was induced by intravenous injection of Con A (15 mg/kg) and plasma alanine aminotransferase (ALT), MIP-2 levels were determined and histological assessment of the liver was performed. Anti-mouse MIP-2 antibody was intravenously administered 30 min before Con A injection. Results: Plasma ALT level significantly elevated and reached a maximum at 8 h after Con A injection. Plasma MIP-2 level was also elevated and reached peak value at 2 h after Con A injection. The elevated ALT level by Con A injection was significantly inhibited by MIP-2 antibody. The elevated plasma MIP-2 level after Con A injection was significantly reduced by TNF-a antibody, and MIP-2 was induced in plasma after recombinant TNF-a injection. Hepatic necrosis and infiltration of neutrophils were observed after Con A injection, and these histological changes were attenuated by MIP-2 antibody. Conclusion: These findings suggest that Con A induces TNF-a release, and this TNF-a stimulates MIP-2 induction, at least partially contributing to the liver injury mediated through the recruitment of neutrophils