J. Yamate et al., Macrophage populations and apoptotic cells in the liver before spontaneoushepatitis in Long-Evans Cinnamon (LEC) rats, J COMP PATH, 120(4), 1999, pp. 333-346
Citations number
39
Categorie Soggetti
Veterinary Medicine/Animal Health","Medical Research Diagnosis & Treatment
The inbred mutant strains of Long-Evans Cinnamon (LEC) rats spontaneously d
evelops acute hepatitis as a result of abnormal copper accumulation, follow
ed by chronic hepatitis, cholangiofibrosis and hepatocellular carcinoma. To
shed some light on the role of macrophages in the liver failure, immunohis
tochemical methods were used to investigate the kinetics of macrophage popu
lations in the liver of male LEC rats, in relation to the appearance of myo
fibroblastic cells and hepatocyte apoptosis. Rats examined at 24 weeks of a
ge and moribund rats killed at 22-25 weeks of age had increased serum conce
ntrations of aspartate aminotransferase and alanine aminotransferase, with
jaundice and histological changes indicative of hepatic failure, whereas ra
ts examined at 8, 12, 16 or 20 weeks old showed no such abnormal findings.
Immunolabelling with ED1 (a monoclonal antibody recognizing rat macrophages
) and ED2 (a monoclonal antibody specific for rat resident macrophages) rev
ealed that numbers of blood monocyte-derived macrophages and Kupffer cells
began to increase markedly at 16 weeks of age (before the onset of hepatiti
s). However, alpha-smooth muscle actin (SMA)-positive myofibroblastic cells
(modulated perisinusoidal cells) and hepatocyte apoptosis, demonstrable by
the TUNEL method, were rarely seen at 8, 12; 16, 20 or 24 weeks. There was
no close relationship between macrophage expansion and the appearance of m
yofibroblastic cells or hepatocyte apoptosis. In moribund rats, only a felv
Sn IA-positive cells were seen in the periportal zones; hepatocytes underg
oing apoptosis increased in number, and macrophages engulfing apoptotic bod
ies were observed occasionally, suggesting that apoptosis was related to he
patic failure as an early event. In addition, immunohistochemical examinati
on demonstrated abnormal deposits of laminin along the sinusoids from 20 we
eks, as an initial extracellular matrix protein in LEC rat livers. (C) 1999
W.B. Saunders Company Limited.