Prostaglandin-E, increases in liver tissue after partial hepatectomy and stimulates DNA synthesis in primary cultures of hepatocytes. This study evaluated the capacity of Kupffer cells isolated at various intervals after partial hepatectomy to produce prostaglandin E, in response to bacterial endotoxin. This stimulator of Kupffer cells is a normal endogenous component of portal venous blood. After partial hepatectomy (6 to 48 hr), when hepatic regeneration rates were greatest, regenerating liver Kupffer cells demonstrated a significantly greater capacity to produce prostaglandin E, in response to bacterial endotoxin than did equal numbers of Kupffer cells from timematched, sham-operated control animals. However, by 12 days after partial hepatectomy, when liver mass had been more than 83% restored, regenerating liver Kupffer cell prostaglandin E, production had decreased to levels produced by sham KC. We postulate that high levels of Kupffer cell-derived prostaglandin E, provide a critical paracrine signal fundamental to the initiation and control of growth by neighboring hepatocytes during liver regeneration. (HEPATOLOGY 1991; 14:368-372.)
During mammalian liver regeneration after partial hepatectomy, rapid cell proliferation occurs in the remaining hepatic tissue so that within 10 to 14 days, the liver regains its original size (1). Despite extensive investigation, the mechanisms that initiate, maintain and terminate this intrinsic regenerative process are not well understood. Studies searching for a "trigger" substance have implicated portal-derived hepatotrophic factors (2), humoral factors (3) and liver-derived growth factors (4) in hepatic regeneration. Although these products may initiate regeneration, they fail to explain how and why growth ceases when hepatic mass is restored.
Prostaglandins (PGs) have been shown to stimulate hepatocyte DNA synthesis and proliferation during hepatic regeneration (5). MacManus and Braceland (6)