Abstracts
1997 Digestive Disease Week

Kupffer cell-mediated inhibition on liver regeneration after combined liver and pancreas resection.

M Unno, M Suzuki, T Rikiyama, T Uchiyama, K Fukuhara, S Matsuno. The First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.

Recently, hepato-pancreato-duodenectomy has been performed in some cases of bile duct carcinoma. However, this procedure causes liver damage and can be a factor of postoperative liver failure. The aim of this study is to investigate the mechanism of the inhibitory effect of combined resection of liver and pancreas on liver regeneration in rats. Methods: Animal experiments. Male SD rats were subjected to 70% hepatectomy and 70% pancreatectomy (HPx) or 70% hepatectomy alone (Hx). The labelling index of the liver was evaluated by BrdU incorporation in vivo. In vitro experiments. Hepatocyte (HC) and Kupffer cells (KC) were isolated by perfusion and digestion with collagenase. HC (2.5 x 10⁵) and KC (1 x 10⁶) were co-cultured in WE media with 10% portal sera from operated rats for 24 hours, then the medium was changed to serum-free WE medium containing 10 ng/ml EGF. [³H]-thymidine was added from 48 to 72 hours and the [³H]-thymidine incorporation was measured. KC-condition media were prepared after stimulation with portal sera from operated rats. HC were cultured with KC-conditioned media and the [³H]-thymidine incorporation was measured as described above. Results: 1) Regenerated liver weight of HPx was significantly lower than that of Hx. 2) Labelling index of regenerated liver in HPx (14.8±2.3%) was significantly lower than that of Hx (23.5±6.7%) at 24h hours after operation. 3) Portal serum obtained from one hour after HPx had a inhibitory effect on DNA synthesis in HC-KC (38% inhibition compared to Hx, p<0.005). 4) KC-conditioned medium, which was stimulated by the portal serum obtained from one hour after HPx, inhibited DNA synthesis of HC (39% inhibition compared to Hx, p<0.05). 5) The inhibitory effect of KC-conditioned medium was completely abolished after incubation at 56° C for 30 min. Conclusions: These results clearly indicate the existence of 'growth inhibitory factor' in portal serum after HPx. This heat-labile growth inhibitory factor was released from Kupffer cells stimulated by portal serum after HPx, and would appear to act on hepatocyte in a paracrine manner. We are now further characterizing the entity of the factor by biochemical methods in protein level.