BINDING CHARACTERISTICS OF SCAVENGER RECEPTORS ON LIVER ENDOTHELIAL AND KUPFFER CELLS FOR MODIFIED LOW-DENSITY LIPOPROTEINS

Previous studies showed that both endothelial and Kupffer cells contai n specific recognition sites of oxidized low-density lipoprotein (OxLD L), in addition to recognition sites which recognize OxLDL and acetyla ted LDL (AcLDL). We have determined the binding characteristics of the recognition sites for OxLDL on Kupffer cells and endothelial cells (O xLDL-specific binding-site) in comparison to the recognition site for AcLDL on endothelial cells, which recognizes both AcLDL and OxLDL (Ac/ OxLDL binding site). The capacity of Kupffer cells to bind OxLDL (B-ma x = 779 ng of I-125-OxLDL/mg of cell protein; K-d = 6 mu g/ml) was com parable to the binding-capacity of endothelial cells (B-max = 803 ng o f I-125-OxLDL/mg of cell protein; K-d = 5 mu g/ml). The effect of net charge of modified LDL on its affinity for the recognition sites on Ku pffer and endothelial cells was evaluated using competition studies. T he affinity of AcLDL for the Ac/OxLDL binding site was greatly increas ed from 460 mu g/ml to 4 mu g/ml with increasing extent of modificatio n and thus net charge. The Ac/OxLDL binding-site on endothelial cells also displayed an increased affinity towards LDL with an increasing de gree of oxidation. The affinity of OxLDL for the Ac/OxLDL binding-site appeared to be about 4-fold higher than that of AcLDL with a similar extent of modification. At higher degrees of oxidation of LDL, the aff inity for the OxLDL-specific site on endothelial and Kupffer cells was also strongly enhanced; the OxLDL-specific binding-site possesses a h igher affinity for mildly oxidized LDL as compared with the Ac/OxLDL b inding-site. It is concluded that recognition of OxLDL by both the OxL DL-specific binding-site and the Ac/OxLDL binding-site on liver endoth elial and Kupffer cells depends on the net negative charge of modified LDL. The similarity in binding pattern of these binding sites makes i t likely that the newly described 95 kD OxLDL binding protein on Kupff er cells [Y. B. De Rijke and Th. J. C. van Berkel, J. Biol. Chem. (199 4), 269, 824-827] contains a recognition site with similar structural elements as described earlier for scavenger receptors.