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

Abstract

Addition of the phospholipids 1‐O‐hexadecyl‐2‐arachidonoyl‐sn‐glycero‐3‐phosphocholine (PLE) and 1‐O‐hexadecyl‐2‐desoxy‐2‐amino‐arachidonoyl‐sn‐glycero‐3‐phosphocholine (PLA) to [¹²⁵I]LDL and subsequent Cu²⁺‐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.