Macrophage inflammatory protein-2 induced by TNF-alpha plays a pivotal role in concanavalin A-induced liver injury in mice.
OBJECTIVE
Macrophage inflammatory protein-2 (MIP-2), one of the CXC chemokines, is involved in the recruitment of neutrophils in several tissue injuries. In this study, we investigated the 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
The plasma ALT level significantly elevated and reached a maximum at 8 h after Con A injection. The plasma MIP-2 level was also elevated and reached a peak value at 2 h after Con A injection. The elevated ALT level by Con A injection was significantly inhibited by the MIP-2 antibody. The elevated plasma MIP-2 level after Con A injection was significantly reduced by the tumor necrosis factor alpha (TNF-alpha) antibody, and MIP-2 was induced in plasma after recombinant TNF-alpha injection. Hepatic necrosis and infiltration of neutrophils were observed after Con A injection, and these histological changes were attenuated by the MIP-2 antibody.


CONCLUSIONS
These findings suggest that Con A induces TNF-alpha release, and this TNF-alpha stimulates MIP-2 induction, at least partially contributing to the liver injury mediated through the recruitment of neutrophils.
Nakamura
K
K
Second Department of internal Medicine, Asahikawa Medical College, Japan. kimihide@asahikawa-med.ac.jp
Okada
M
M
Yoneda
M
M
Takamoto
S
S
Nakade
Y
Y
Tamori
K
K
Aso
K
K
Makino
I
I
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D003208:Concanavalin A / Q000633:toxicity*; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D000906:Antibodies; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D000410:Alanine Transaminase