NDLI: Coordinate stimulation of macrophages by microparticles and TLR ligands induces foam cell formation.

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Coordinate stimulation of macrophages by microparticles and TLR ligands induces foam cell formation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Larregina, Adriana T. Salter, Russell D. Keyel, Peter A. Tkacheva, Olga A.
Description	Country affiliation: United States Author Affiliation: Keyel PA ( Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15260, USA. pak55@pitt.edu)
Abstract	Aberrant activation of macrophages in arterial walls by oxidized lipoproteins can lead to atherosclerosis. Oxidized lipoproteins convert macrophages to foam cells through lipid uptake and TLR signaling. To investigate the relative contributions of lipid uptake and TLR signaling in foam cell formation, we established an in vitro assay using liposomes of defined lipid compositions. We found that TLRs signaling through Toll/IL-1R domain-containing adapter inducing IFN-ß promoted foam cell formation by inducing both NF-κB signaling and type I IFN production, whereas TLRs that do not induce IFN, like TLR2, did not enhance foam cell formation. Addition of IFN- to TLR2 activator promoted robust foam cell formation. TLR signaling further required peroxisome proliferator-activated receptor , as inhibition of peroxisome proliferator-activated receptor blocked foam cell formation. We then investigated the ability of endogenous microparticles (MP) to contribute to foam cell formation. We found that lipid-containing MP promoted foam cell formation, which was enhanced by TLR stimulation or IFN- . These MP also stimulated foam cell formation in a human skin model. However, these MP suppressed TNF- production and T cell activation, showing that foam cell formation can occur by immunosuppressive MP. Taken together, the data reveal novel signaling requirements for foam cell formation and suggest that uptake of distinct types of MP in the context of activation of multiple distinct TLR can induce foam cell formation.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1200828
Journal	The Journal of Immunology
Issue Number	9
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Differentiation Immunology Cell-derived Microparticles Foam Cells Metabolism Macrophages Toll-like Receptors Animals Bone Marrow Cells Pathology Cell Line, Tumor Cells, Cultured Hela Cells Ligands Lipid Metabolism Melanoma, Experimental Mice Mice, Inbred C57bl Mice, Knockout Signal Transduction Physiology Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Coordinate Stimulation of Macrophages by Microparticles and TLR Ligands Induces Foam Cell Formation 1

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Coordinate stimulation of macrophages by microparticles and TLR ligands induces foam cell formation.

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