‘Danger’ effect of low‐density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells

Summary Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous ‘dangerous’ signals that can...

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Published in:Clinical and experimental immunology 2007-09, Vol.149 (3), p.543-552
Main Authors: Zaguri, R., Verbovetski, I., Atallah, M., Trahtemberg, U., Krispin, A., Nahari, E., Leitersdorf, E., Mevorach, D.
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Antigens, CD - blood
Apoptosis - drug effects
B7-2 Antigen - blood
Biological and medical sciences
CD83 Antigen
Cell Differentiation - drug effects
Cell Differentiation - immunology
Cells, Cultured
danger
dendritic cells
Dendritic Cells - drug effects
Fundamental and applied biological sciences. Psychology
HLA-DR Antigens - blood
Humans
Immunoglobulins - blood
inflammation
LDL
Lipoproteins, LDL - pharmacology
Membrane Glycoproteins - blood
Molecular biophysics
oxLDL
Phagocytosis - immunology
Receptors, CCR7
Receptors, Chemokine - blood
Translational Studies
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Summary:Summary Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous ‘dangerous’ signals that can induce dendritic cell maturation. We have found that autologous plasma contains danger signals that induce up‐regulation of major histocompatibility complex (MHC) class II and co‐stimulatory molecules in immature DCs (iDCs). The objective of this study was to determine whether low‐density lipoprotein (LDL) and/or oxidized LDL (oxLDL) constitute danger signals, and to assess the effect of exposure to LDL and oxLDL following monocyte differentiation into iDCs in lipoprotein‐deficient serum (LPDS). IDCs were generated in the presence of autologous plasma or LPDS. Expression of maturation and migration molecules was evaluated using flow cytometry, and morphology was assessed by light microscopy. Pro‐ or anti‐apoptotic effect was determined using annexin V and propidium iodide binding. Phagocytosis of apoptotic cells was evaluated using autologous plasma or LPDS. LDL and oxLDL were clearly able to slightly up‐regulate levels of HLA‐DR and co‐stimulatory molecule CD86. High oxLDL concentrations (50–100 µg/ml) were associated with expression of additional maturation molecules. Moreover, iDCs that were prepared in LPDS showed partial maturation following exposure to LDL and oxLDL, and improved tolerogenic apoptotic cell uptake. This study suggests that oxLDL, and to some extent LDL, are at least partly responsible for the iDC ‘danger’ response induced by autologous plasma.
ISSN:0009-9104
1365-2249
DOI:10.1111/j.1365-2249.2007.03444.x