Regulation of acetylated low density lipoprotein uptake in macrophages by pertussis toxin-sensitive G proteins

Class A scavenger receptors (SR-A) mediate the uptake of modified low densi ty lipoprotein (LDL) by macrophages, Although not typically associated with the activation of intracellular signaling cascades, results with peritonea l macrophages indicate that the SR-A ligand acetylated LDL (AcLDL) promotes activation of cytosolic kinases and phospholipases. These signaling respon ses were blocked by the treatment of cells with pertussis toxin (PTX) indic ating that SR-A activates G(i/o)-linked signaling pathways, The functional significance of SR-A-mediated G(i/o) activation is not clear, In this study , we investigated the potential role of G(i/o), activation in regulating SR -A-mediated lipoprotein uptake. Treatment of mouse peritoneal macrophages w ith PTX decreased association of fluorescently labeled AcLDL with cells, Th is inhibition was dependent on the catalytic activity of the toxin confirmi ng that the decrease in AcLDL uptake involved inhibiting G(i/o) activation. In contrast to the inhibitory effect on AcLDL uptake, PTX treatment did no t alter beta-VLDL-induced cholesterol esterification or deposition of chole sterol, The ability of polyinosine to completely inhibit AcLDL uptake, and the lack of PTX effect on B-VLDL uptake, demonstrated that the inhibitory e ffect is specific for SR-A and not the result of non-specific effects on li poprotein metabolism. Despite having an effect on an SR-A-mediated lipoprot ein uptake, there was no change in the relative abundance of SR-A protein a fter PTX treatment. These results demonstrate that activation of a PTX-sens itive G protein is involved in a feedback process that positively regulates SR-A function. Post. Regulation of acetylated low density lipoprotein upta ke in macrophages by pertussis toxin-sensitive G proteins.