Oxidative tyrosylation of high density lipoproteins impairs cholesterol efflux from mouse J774 macrophages: role of scavenger receptors, classes A and B

Studies were designed to test whether tyrosylation of high-density lipoprotein (HDL_T) modifies its metabolic features. HDL_Twas less effective than native HDL in promoting cholesterol efflux from J774-AI macrophages. Cell association with fluorescent HDL_T-apolipoprotein and the uptake of HDL_T-[³H]cholesteryl hexadecyl ether were enhanced by 50% in comparison with native HDL. In addition, neutral cholesterol ester hydrolase (nCEH) activity in J774-AI, which controls the hydrolysis of cholesteryl ester stores to provide free cholesterol for cellular release,declined in the presence of HDL_T. In vitro displacement experiments revealed the ability of HDL_T to compete with oxidized and acetylated LDL, known as ligands of scavenger receptor (SR) class B type I/II. Similarly, treatment with a blocking antibody to SR-BI/II reduced the cell association of HDL_T and native HDL by 50%. The addition of polyinosinic acid, an inhibitor of SR class A, reduced the cell association of HDL_T without affecting that of native HDL. These findings provide evidence that HDL_T can compete with modified LDL, bind SR-BI/BII and internalize cholesterol ester. Furthermore, the impaired capacity of HDL_T in promoting cholesterol efflux from J774-AI was accompanied by diminished nCEH and enhanced recognition by SR-AI/II, which appears to involve the transport of cholesterol into cells.