Low density lipoprotein metabolism in human macrophages stimulated with microbial or microbial-related products

To determine whether stimulation of macrophages with products related to, or released as a consequence of, infectious processes could play a role in inducing the formation of foam cells, we studied the metabolism of native and acetylated low density lipoprotein (LDL) by human macrophages stimulated with lipopolysaccharide (LPS), muramyl dipeptide (MDP), polyinosinic:polycytidilic acid (Poly I:Poly C) and gamma-interferon. Cholesteryl ester (CE) synthesis by macrophages stimulated with LPS, MDP and Poly I:Poly C was markedly increased when the cells were incubated with native LDL (p less than 0.05). When incubated with acetylated LDL, LPS-stimulated macrophages showed a depression in CE synthesis (p less than 0.05). When incubated with acetyl-LDL, macrophages stimulated with Poly I:Poly C and gamma interferon showed a significant increase (p less than 0.05) in CE synthesis. The increase in CE synthesis by LPS-stimulated macrophages exposed to native LDL and by gamma-interferon-stimulated macrophages exposed to acetylated LDL was paralleled by an increase in cholesterol ester mass. The increase in CE synthesis and accumulation observed in LPS-stimulated macrophages incubated with native LDL seems to be due to an increase in the receptor mediated uptake of LDL. LPS inhibited and gamma-interferon activated the expression of the scavenger pathway in human macrophages. This may explain the changes observed in CE synthesis and accumulation when macrophages activated by the above stimuli were incubated with acetylated LDL. In conclusion, activation of human macrophages by some products released during, or as a consequence of, infectious processes led to an increase in CE synthesis and accumulation that may be relevant to the formation of "foam cells".