REMNANT HIGH-DENSITY LIPOPROTEIN(2) PARTICLES PRODUCED BY HEPATIC LIPASE DISPLAY HIGH-AFFINITY BINDING AND INCREASED ENDOCYTOSIS INTO A HUMAN HEPATOMA-CELL LINE (HEPG(2))

We had previously shown that hepatic lipase plays a prominent role in promoting the generation of pre-beta HDL particles from triglyceride r ich HDL2, leaving an a-HDL particle of decreased size that was named ' 'remnant HDL2'' [Barrans, A., et al. (1994) J. Biol. Chem. 269, 11572- 11577]. Interestingly, this remnant HDL2 was rapidly cleared by the li ver, suggesting a particularly high affinity of those remnant HDL2 for liver cells. In the present study, we attempted to characterize the i nteraction of remnant HDL2 with HepG(2) cells, as compared to those of native triglyceride rich HDL2. Two main observations were made. First , while triglyceride rich HDL2 particles were able to bind only the lo w-affinity binding sites, the remaining particle generated after hepat ic lipase lipolysis the remnant HDL2 was further able to bind to the h igh-affinity binding sites. Competition experiments indicate that thes e two remnant HDL2 binding sites were the same as the two HDL3 binding sites previously described [Barbaras, R., et al. (1994) Biochemistry 33, 2335-2340]. This is the first observation on the remodelling depen dence of HDL binding onto hepatocytes. Second, following binding on th ose two binding sites, the remnant HDL2 were faster internalized and i n higher amounts than the native triglyceride rich HDL2. All together, these observations suggest that the continuous remodeling of HDL indu ces different binding and internalization characteristics of the HDL p articles and that the high-affinity HDL binding sites might trigger th e internalization of apo HDL through the low-affinity binding sites.