Susceptibility of phospholipids of oxidizing LDL to enzymatic hydrolysis modulates uptake by P388D1 macrophage-like cells.

Addition of the phospholipids 1-O-hexadecyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PLE) and 1-O-hexa-decyl-2-desoxy-2-amino-arachidonyl-sn-glycero-3- phosphocholine (PLA) to [125I]LDL and subsequent Cu(2+)-induced oxidation result in significant differences in protein modification and uptake by P388D1 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.