Stimulation of macrophage DNA synthesis by polyanionic substances through binding to the macrophage scavenger receptor.

We previously demonstrated that ligands of macrophage scavenger receptors such as acetylated low density lipoprotein (LDL), oxidized LDL and advanced glycation-end products (AGE) of the Maillard reaction induce the growth of peritoneal exudate macrophages, and that the activity of AGE is inhibited by the presence of an antibody for granulocyte/macrophage colony-stimulating factor (GM-CSF). To evaluate the suggested role of the scavenger receptor in the induction of macrophage growth, we compared the effect of various polyanionic compounds which were reported to either have or not to have competent activity for the binding of acetylated LDL to scavenger receptors on macrophage DNA synthesis. Among the polyanions exhibiting such activity, polyguanilic acid (poly G) and dextran sulfate strongly augmented macrophage DNA synthesis, although they did not increase macrophage cell number. On the other hand, polyanions which are not ligands for the scavenger receptors did not show a significant augmenting effect, suggesting that the binding of polyanions to the scavenger receptor is important but not, by itself, sufficient. The augmentation of DNA synthesis in macrophages cultured with dextran sulfate or poly G was inhibited by the co-presence of anti-GM-CSF antibody, suggesting that the reaction is mediated by GM-CSF. However, dextran sulfate did not augment the production of GM-CSF in macrophages. Therefore, GM-CSF spontaneously present in macrophages might be a prerequisite for the induction of DNA synthesis.