Kupffer cell depletion shifts the balance of growth-modulatory cytokines to promote hepatocyte proliferation: [formula omitted] Dept. of Medicine, Johns Hopkins University, Baltimore, MD

Abstract

Proliferating lipocytes (fat-storing cells or perisinusoidal stellate cells of the liver) were detected by in vivo incorporation of bromodeoxyuridine (BrdU) in an experimental model of cirrhosis in the rat by dimethylnitrosamine. Lipocytes were identified by sequential double immunohistochemical staining on frozen sections using anti-desmin antibodies as a marker of cytoplasmic intermediate filaments followed by anti-BrdU antibodies to identify S-phase nuclei in animals treated for 7, 14 or 21 days. The number of desmin-positive (lipocytes) and desmin-negative (Kupffer and endothelial cells) sinusoidal cells incorporating BrdU was recorded. The labelling index of lipocytes was calculated as the percentage of BrdU-labelled desmin-positive cells with respect to total number of lipocytes. In control animals, when the total number of lipocytes was 153.9 ± 11/mm2 (mean ± 1 S.E.) the number of desmin-posilive S-phase sinusoidal cells never exceeded 6.8 ± 1.2/mm2 with a maximum labelling index of 4.3 ± 0.5%. At 7 days of treatment, the values were respectively 236 ± 26.5/mm2, 53.2 ± 5.9/mm2 and 22.6 ± 0.5% (p < 0.001 vs. controls), while, at 21 days they were 272.5 ± 21.2/mm2, 23.3 ± 4.0/mm2 and 8.5 ± 1.1% respectively (p < 0.01). These results show that hyperplasia of lipocytes represents an early reaction to dimethylnitrosamine-induced liver injury. The local accumulation of lipocytes appear to occur in areas where fibrous septa develop later on.