MACROPHAGE FOAM CELL IS ATTRIBUTE OF INFLAMMATION: MECHANISMS OF FORMATION AND FUNCTIONAL ROLE
Transformation of macrophages into foam cells is traditionally considered in the context of atherogenesis with the assumption that lipid accumulation is a consequence of oxidized low density lipoprotein (oxLDL) uptake through scavenger receptors (SR). However, it has been shown that excessive oxLDL uptake induces compensatory mecha" nisms of cholesterol removal from macrophages. Maintenance of lipid homeostasis is control by system lipid sensors, the functional regulation of which is reprogrammed by inflammation leading to formation of foam cell phenotype without the participation of SR. The rise of inflammatory responsiveness in M1 macrophages is associated with the suppression of LXR and PPAR, expression of its target genes, induction of expression of genes concerned with fatty acid and cholesterol metabolism controlled by SREBP1c and SREBP2, respectively, lipid droplet"associated protein expression, activation of macropinocytosis, synthesis and secretion of LXR and PPAR endogenous ligands, and devel" opment of apoptosis. In this review the role of foam cells in development and resolution of acute inflammatory response and the mechanisms of their formation from macrophages infected by various bacterial and viral pathogens leading to chronic evolution of inflammation and the relevance of LXR and PPAR as therapeutic targets for chronic infectious and inflammatory diseases are discussed.