Uptake of chylomicron remnants and hepatic lipase-treated chylomicrons by a non-transformed murine hepatocyte cell line in culture

AML 12 is a recently established differentiated, non-transformed hepatocyte cell line derived from mice transgenic for transforming growth factor α (Wu et al. (1994) Proc. Natl. Acad. Sci. 91, 674-678). The ability of these cells to take up [³H]cholesterol-labeled in vivo-generated chylomicron remnants, as well as [³H]cholesterol-labeled chylomicrons treated with hepatic lipase in vitro was investigated. Both types of lipoprotein particles were taken up by the AML hepatocytes at a much faster rate than intact chylomicrons, and in a saturable and specific manner. Chylomicrons treated with hepatic lipase in vitro competed with in vivo-generated chylomicron remnants for uptake by the AML hepatocytes, and the uptake of both types of lipoproteins was inhibited by lactoferrin, suggesting that they share the same process of cellular recognition and uptake. It is suggested that hepatic lipase-treated chylomicrons may be valuable in studies aimed at gaining a better understanding of the processes involved in the hepatic recognition and uptake of chylomicron remnants. AML hepatocytes, which can be maintained as replicating, untransformed, and differentiated under standard culture conditions, may be useful and practical for such studies.