The metabolism of native and malondialdehyde-altered low density lipoproteins by human monocyte-macrophages.
We have recently shown that cultured human monocyte-macrophages degraded 125I-labeled low density lipoprotein (125I-nativeee-LDL) by a saturable high-affinity process with maximal velocity at 25-30 microgram protein/ml (Fogelman et al., 1980, Proc. Nat. Acad. Sci. USA. 77:2214-2218). We now describe studies of the binding of 125I-native-LDL at 4 degrees C and the effects of chloroquine, Ca2+ concentration, and reductive methylation on high-affinity 125I-native-LDL degradation that indicate that native-LDL is processed by the monocyte-macrophages via the classic LDL receptor pathway. The high-affinity degradation of 125I-native-LDL increased substantially when monocyte-macrophages were exposed to the lipoprotein deficient-fraction of serum (LPDS) for periods as brief as 4 hours, and was 25-fold greater than that of lymphocytes. Freshly isolated monocytes that had never been exposed to LPDS also demonstrated high-affinity degradation of 125I-nativ-LDL. When these monocytes were cultured for 7 days in a medium containing native-LDL at a concentration (186 microgram protein/ml) greatly in excess of that apparently needed to saturate the high-affinity process, there was more than a 10-fold increase in 125I-native-LDL high-affinity degradation. LDL modified by treatment with malondialdehyde was processed by a second high-affinity cell surface receptor that appears identical to the "scavenger" receptor that processes acetylated LDL (Goldstein, et al., 1979, Proc. Nat. Acad. Sci. USA. 76: 333-337).
D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008314:Malonates / Q000494:pharmacology*; D008315:Malondialdehyde / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011973:Receptors, LDL
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008314:Malonates; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D008315:Malondialdehyde; D002738:Chloroquine; D002784:Cholesterol; D004492:Edetic Acid