Red blood cells participate in reverse cholesterol transport by mediating cholesterol efflux of high-density lipoprotein and apolipoprotein A-I from THP-1 macrophages.

High-density lipoprotein (HDL) plays a main role in reverse cholesterol transport (RCT), one of the most important functions for preventing atherosclerosis. Recent reports have shown that red blood cells (RBCs) can be associated with RCT, an interaction facilitated by albumin. However, the RCT function of RBCs has not been thoroughly elucidated. In this study, the RCT function of RBCs was assessed using cholesterol efflux capacity (CEC) assays, in which [3H]-labeled cholesterol-loaded human acute monocytic leukemia (THP-1) macrophages were incubated with RBCs as a cholesterol acceptor in the presence or absence of HDL or its main component protein apolipoprotein A-I (apoA-I). The CEC of RBCs was found to be dose dependent, enabling uptake of cholesterol from THP-1 macrophages through apoA-I and HDL, and directly from apoA-I and HDL in medium without the presence THP-1 macrophages. Moreover, RBCs could exchange cholesterol with HDL in a bidirectional manner but could only exchange cholesterol with apoA-I in a single direction. Although albumin promoted the movement of cholesterol, synergistic effects were not observed for both apoA-I and HDL, in contrast to previous findings. These results strongly suggested that RBCs may play important roles in RCT by mediating cholesterol efflux as temporary cholesterol storage.