Involvement of second messengers in lipopolysaccharide stimulation of low density lipoprotein uptake by macrophages

Macrophage degradation of low density lipoprotein (LDL) was shown to be increased in lipopolysaccharide (LPS)-stimulated cells. The involvement of second messengers in this phenomenon was studied. Preincubation of J-774A.1 macrophages with the protein kinase C (PKC) inhibitors D-sphingosine or staurosporine did not significantly affect the stimulatory action of LPS. Similarly, J-774A.1 macrophage-like cell line, incubation with 1,2-dioleoyl-sn-glycerol had no effect on cellular degradation of LDL. However, preincubation of J-774A.1 macrophages with dibutyryl cyclic adenosine monophosphate (50 microM dB-cAMP) led to a 51% increase in the cellular degradation of LDL. Analysis of cAMP content in LPS-stimulated cells revealed a 59% elevation in its cellular content in comparison to non-stimulated cells. Our results suggest that LPS stimulation of macrophage uptake of LDL occurs via the cAMP pathway and not via PKC activation. These results may contribute to understanding of the mechanism by which activated macrophages accumulate cholesterol.