LIPOPROTEIN-LIPASE REDUCES SECRETION OF APOLIPOPROTEIN-E FROM MACROPHAGES

Macrophages are a significant source of lipoprotein lipase (LPL) and a polipoprotein E (ape E) in the developing arterial wall lesion, and ea ch of these proteins can importantly modulate lipid and lipoprotein me tabolism by arterial wall cells, LPL and apo E share a number of cell surface binding sites, including proteoglycans, and we have previously shown that proteoglycans are important for modulating net secretion o f apoprotein E from macrophages. We therefore evaluated a potential ro le for LPL in modulating net secretion of macrophage-derived apo E, In pulse-chase experiments, addition of LPL during the chase period prod uced a decrease in secretion of apoprotein E from human monocyte-deriv ed macrophages, from the human monocytic THP1 cell line, and from J774 cells transfected to constitutively express a human apo E cDNA, LPL s imilarly reduced apo E secretion when it was prebound to the macrophag e cell surface at 4 degrees C, A native LPL particle was required to m odulate apo E secretion; addition of monomers and aggregates did not p roduce the same effect, Depletion of cell surface proteoglycans by a 7 2-h incubation in 4-methylumbelliferyl-beta-D-xyloside did not attenua te the ability of LPL to reduce apo E secretion, However, addition of receptor-associated protein attenuated the effect of LPL on apo E secr etion, Although LPL could mediate removal of exogenously added apo E f rom the culture medium, detailed pulse-chase analysis suggested that i t primarily prevented release of newly synthesized apo E from the cell layer, Cholesterol loading of cells or antibodies to the low density lipoprotein receptor attenuated LPL effects on apo E secretion, We pos tulate that LPL sequesters endogenously synthesized apo E at the cell surface by a low density lipoprotein receptor-dependent mechanism, Suc h post-translational regulation of macrophage apo E secretion by LPL c ould significantly influence apo E accumulation in arterial vessel wal l lesions.