Direct cell-to-cell contact between Kupffer cells and hepatocytes augmentsendotoxin-induced hepatic injury

This study focuses on the importance of direct contact between Kupffer cell s (KCs) and hepatocytes (HCs) during the hepatic inflammatory response usin g an in vitro approach. The lipopolysaccharide (LPS)-induced inflammatory r esponse in monocultures of porcine HCs and KCs were compared with coculture s prepared either with direct contact between KCs and HCs (DC cocultures) o r without direct contact using cell culture membrane inserts. Our data show that DC cocultures exhibited the highest production of tumor necrosis fact or (TNF)-alpha, interleukin-6, and nitric oxide (NO) compared with the othe r cultures. Immunohistochemical studies revealed that TNF-alpha was exclusi vely produced by KCs, whereas HCs were responsible for NO production after LPS stimulation. Biotransformation capacity, as determined by cytochrome P- 450 and UDP glucuronosyl transferase enzyme activities, was most significan tly decreased in DC cocultures. These results provide evidence that direct contact between KCs and HCs favors the extensive TNF-alpha production by KC s but in turn affects HC functionality and viability. These findings sugges t that direct contact between KCs and HCs plays a key role in the developme nt of a fulminating hepatic inflammatory response.