Effects of Gadolinium Chloride (GdCl3) on the Appearance of Macrophage Populations and Fibrogenesis in Thioacetamide-Induced Rat Hepatic Lesions

Macrophages infiltrating injured tissue play an important part in fibrogenesis. To shed light on the functional roles of macrophages, we investigated the appearance of macrophage populations in thioacetamide (TAA)-induced rat hepatic lesions, with or without pretreatment with GdCl3, a chemical capable of inhibiting Kupffer cell functions. In the GdCl3+TAA group rats received a single intraperitoneal injection of GdCl3 (7.5 mg/kg body weight) and, after 24 h, a single intravenous injection of TAA (300 mg/kg body weight). Rats in the TAA group received TAA only. Rats in both groups were examined on post-TAA injection (PTI) days 3, 5, and 7. In the TAA group, on PTI day 3, when TAA-induced hepatocyte injury was particularly prominent, the number of macrophages peaked, subsequently decreasing until PTI day 7. As compared with the TAA group, the GdCl3+TAA group showed significantly decreased numbers of ED1-immunolabelled cells (exudate macrophages) and ED2-immunolabelled cells (Kupffer cells) on PTI days 3, 5, and 7, and OX6-immunolabelled cells (antigen-presenting macrophages) on PTI days 3 and 5. Although less strikingly, the numbers of α-smooth muscle actin-positive myofibroblasts and fibrotic areas were decreased in the GdCl3+TAA group. By RT-PCR, the expression of TGF-β1 mRNA was suppressed on PTI days 3 and 7 in the GdCl3+TAA group, and the suppressed expression was confirmed in vitro by treating rat macrophage-like cells (HS-P) with 1% GdCl3. The study showed that GdCl3 treatment decreased the numbers of macrophages appearing in hepatic lesions and inhibited TGF-β1 mRNA expression in macrophages. Decreased numbers of macrophages may contribute to improvement of hepatic fibrosis.