CONFORMATIONAL-CHANGES IN OXIDIZED LDL RECOGNIZED BY MOUSE PERITONEAL-MACROPHAGES

Mouse peritoneal macrophages have been considered to recognize and tak e up oxidized LDL by a scavenger receptor. However, it is still unknow n what conformational changes in oxidized LDL contribute to recognitio n by the macrophage scavenger receptor. In the present study, it was s hown that the amount of oxidized LDL taken up by macrophages correlate d well with the fluorescence intensity formed in oxidized LDL. The aut ofluorescent products generated in oxidized LDL were characterized by Ex:365 nm Em:430 nm, and the intensity of the fluorescence was reduced at base pH, and restored by adjusting the pH to neutral. The characte ristics of the fluorescent products indicate that a Schiff base struct ure was formed in oxidized LDL. Oxidized LDLs were fractionated into n ative size and aggregated large particles with HPLC by monitoring fluo rescence, It was demonstrated that macrophages ingest selectively or p referentially aggregated oxidized LDL, but not native size oxidized LD L. The incorporation of aggregated oxidized LDL was remarkably suppres sed by heparin and cytochalasin B. These results suggest that mouse pe ritoneal macrophages recognize the conformational changes in oxidized LDL related to the formation of a Schiff base structure with increasin g autofluorescence, and ingest selectively aggregated large particles in oxidized LDL in a phagocytic process.