SUSCEPTIBILITY OF PHOSPHOLIPIDS OF OXIDIZING LDL TO ENZYMATIC-HYDROLYSIS MODULATES UPTAKE BY P388D(1) MACROPHAGE-LIKE CELLS

Addition of the phospholipids 1-O-hexadecyl-2-arachidonyl-sn-glycero-3-phosphocholine (PLE) and 1-O-hexadecyl-2-desoxy-2-amino-arachidonoyl-sn-glycero-3-phosphocholine (PLA) to [I-125]LDL and subsequent Cu2+-induced oxidation result in significant differences in protein modification and uptake by P388D(1) macrophage-like cells, PLE-treated LDL is ingested at a 1.27-fold rate compared to PLE-treated LDL and displays enhanced electrophilic mobility, Similar results (1.43-fold enhanced uptake of LDL preloaded with PLE) are obtained when the uptake of phospholipid-enriched oxLDL particles are examined, The preference for ingestion as well as protein modification of both preparations is, however, reversed under experimental conditions allowing diffusion and inactivation of a fraction of the peroxidation products, These findings suggest that LDL-associated PAF-acetylhydrolase can exert a dual role and, to be protective to LDL, require an appropriate microenvironment, capable of binding certain species of oxidatively fragmented lipids.