[Cocultures between primary parenchymal and nonparenchymal liver cells improve the reliability of results from in...

Conventional homotypic hepatocyte cultures do not include the possible contribution of nonparenchymal liver cells, particularly Kupffer cells, to the pharmacological and toxicological consequences after exposure to xenobiotics. Therefore the exchange of soluble factors between liver cells was investigated in cocultures between primary, freshly isolated cultured rat hepatocytes and Kupffer cells. Cocultures were exposed to endotoxins in combination with phenobarbital, 3-methylcholanthrene or lead. A strong but selective down-regulation of xenobiotic induced cytochrome P450 isoforms was detectable, mediated exclusively by TNFalphareleased from the Kupffer cells. Pb synergistically increased this endotoxin induced TNFalpha-release. The results indicate that cocultures improve the reliability of data obtained from organ specific cell cultures and that they simulate much closer the situation in the intact liver.