Macrophage/foam cell is an attribute of inflammation: Mechanisms of formation and functional role

Transformation of macrophages into foam cells is traditionally considered in the context of atherogenesis, because lipid accumulation is believed to be a consequence of uptake of oxidized low density lipoproteins (oxLDL) through scavenger receptors (SR) of macrophages. However, an excessive uptake o...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2012-04, Vol.77 (4), p.327-338
Main Author: Dushkin, M. I.
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Biosynthesis
Blood lipids
Cholesterol
Foam Cells - immunology
Foam Cells - metabolism
Humans
Inflammation
Inflammation - genetics
Inflammation - immunology
Inflammation - metabolism
Life Sciences
Lipid Metabolism
Low density lipoprotein
Low density lipoproteins
Macrophages - immunology
Macrophages - metabolism
Microbiology
Proteins
Receptors, Scavenger - genetics
Receptors, Scavenger - immunology
Review
Signal Transduction
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Summary:Transformation of macrophages into foam cells is traditionally considered in the context of atherogenesis, because lipid accumulation is believed to be a consequence of uptake of oxidized low density lipoproteins (oxLDL) through scavenger receptors (SR) of macrophages. However, an excessive uptake of oxLDL is recently shown to trigger compensatory mechanisms of cholesterol elimination from macrophages. Maintaining the lipid homeostasis in macrophages is mediated by regulation of a system of lipid sensors, which is reprogrammed under conditions of inflammation leading to formation of foam cell phenotype without involvement of SR. The increase in the inflammatory potential on macrophage polarization into the M1 phenotype is associated with suppression of LXR and PPAR, their target genes, induction of expression of genes responsible for fatty acid and cholesterol metabolism controlled by SREBP1c and SREBP2, proteins associated with lipid inclusions, macropinocytosis activation, secretion of LXR and PPAR endogenous ligands, and development of apoptosis. In this review the role of foam cells in development and resolution of acute inflammation, mechanisms of their formation from macrophages infected by some bacterial and virus pathogens causing chronic inflammation, and the significance of LXR and PPAR as therapeutic targets in chronic infectious and inflammatory diseases are also discussed.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297912040025