Immunopathology of acute galactosamine hepatitis in rats.
Galactosamine hydrochloride induces liver disease in rats that morphologically resembles drug-induced hepatitis in man. In this study we analyzed the character of the inflammatory reaction following the toxic damage resulting from the administration of galactosamine hydrochloride using a broad panel of monoclonal antibodies to lymphocyte subsets and macrophages. Fat-storing cells were identified with a polyclonal anti-desmin antibody. Cellular proliferation was assessed by labeling S-phase cells with the thymidine analog bromodeoxyuridine. Injection of galactosamine hydrochloride was associated with conspicuous hepatocyte necrosis and parenchymal granulocyte influx in the first 24 hr. Thereafter, mononuclear inflammatory cells predominated, mainly T lymphocytes and macrophages, with maximal numbers at 48 hr. The majority of T lymphocytes were CD8-positive cells and were located in the portal tracts and parenchyma. CD4-positive T cells were scarce and confined to the portal tracts. Proliferation of fat-storing cells paralleled hepatocyte regeneration with maximal values after 48 to 72 hr. The temporal relationship between infiltrating mononuclear cells, mainly T lymphocytes of CD8 phenotype and macrophages, fat-storing cell proliferation and hepatic regeneration suggests pathophysiological interactions between these cell types in liver injury in the rat after galactosamine hydrochloride administration.
Jonker
A M
AM
Department of Pathology, University of Groningen, The Netherlands.
Dijkhuis
F W
FW
Kroese
F G
FG
Hardonk
M J
MJ
Grond
J
J
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005688:Galactosamine / Q000009:adverse effects*; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology / Q000473:pathology; D008115:Liver Regeneration; D008264:Macrophages / Q000473:pathology; D008297:Male; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology
D000911:Antibodies, Monoclonal; D005688:Galactosamine