Transcellular biosynthesis of cysteinyl leukotrienes by Kupffer cell-hepatocyte cooperation in rat liver

We previously proposed that an enzymatic cooperation between Kupffer cells and hepatocytes may play an important role in cysteinyl leukotriene (LT) production in rat liver. An in vitro transcellular synthesis cysteinyl LTs by a Kupffer cell-hepatocyte coculture system was characterized here. Kupffer cells alone, with A23187 stimulation, did not generate cysteinyl LTs until supplemented either with isolated hepatocytes or with LTC(4) synthase and glutathione, indicating that Kupffer cells can synthesize LTA(4) but not convert it into LTC(4). In contrast, hepatocytes converted the LTA(4) into cysteinyl LTs and further degraded the cysteinyl LTs. Cysteinyl LT production by the Kupffer cell-hapatocyte coculture system was optimized by addition of 1-3% serum albumin to the culture and by bringing the cell-cell distance closer to less than 3 mu. Tumour necrosis factor also stimulated cysteinyl LT production by the coculture system. From these results, it is expected that the Kupffer cell-hepatocyte transcellular system for cysteinyl LT production actually functions in vivo. (C) 1996 Academic Press Limited