Midzonal necrosis of the liver after concanavalin A-injection.
Concanavalin A (Con A) can induce an immune-mediated hepatitis. Since direct evidence of immune mechanism for this hepatitis is lacking, we employed adoptive transfer to study the mechanism of Con A-induced hepatitis. Intravenous administration of Con A (20 mg/kg) to Balb/c mice was accompanied by elevations of serum alanine aminotransferase (ALT) levels and midzonal necrosis with lymphocyte infiltration in the liver. None of the Balb/c nu/nu mice showed biochemical or pathologic hepatic abnormalities with the same dose of Con A. In the area of midzonal necrosis, CD4-positive T lymphocytes appeared at 24 hr after injection, and then both CD4-positive and CD8-positive T lymphocytes were found at the margin of zonal necrosis at 48 hr. Pretreatment with carrageenan, a potent inhibitor of macrophages, prevented these biochemical and pathologic changes. Mononuclear cells infiltrating in the liver of Balb/c mice 24 hr after priming with Con A were harvested and injected into Balb/c nu/nu mice injected with Con A 24 hr previously. Serum ALT levels elevated and the same pathologic changes observed in Con A-treated Balb/c mice were observed. These changes were not observed when the splenic cells from Con A-treated Balb/c mice were transferred to Con A-treated nude mice. These results suggest that Con A-induced hepatic injury is mediated by macrophages and T lymphocytes sensitized by Con A or its metabolites.
Satoh
M
M
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai.
Kobayashi
K
K
Ishii
M
M
Igarashi
T
T
Toyota
T
T
D019264:Adoptive Transfer; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D003208:Concanavalin A / Q000633:toxicity*; D006520:Hepatitis, Animal / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D007249:Inflammation; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D013154:Spleen
D003208:Concanavalin A; D002351:Carrageenan; D000410:Alanine Transaminase