Dyslipidemia Associated with Atherosclerotic Disease Systemically Alters Dendritic Cell Mobilization

High LDL and/or low HDL are risk factors for atherosclerosis and are also a common clinical feature in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Here, we show that changes in lipid profiles that reflect atherosclerotic disease led to activation of skin murine dendritic cells...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2004-10, Vol.21 (4), p.561-574
Main Authors: Angeli, Véronique, Llodrá, Jaime, Rong, James X., Satoh, Kei, Ishii, Satoshi, Shimizu, Takao, Fisher, Edward A., Randolph, Gwendalyn J.
Format: Article
Language:English
Subjects:
1-Alkyl-2-acetylglycerophosphocholine Esterase - metabolism
Age
Animals
Apolipoproteins
Apolipoproteins E - deficiency
Arteriosclerosis - immunology
Arteriosclerosis - physiopathology
Atherosclerosis
Autoimmune diseases
Cell Movement - immunology
Cholesterol
Cholesterol, HDL - metabolism
Colleges & universities
Dendritic Cells - immunology
Disease
Female
Flow cytometry
Humans
Hyperlipidemias - immunology
Hyperlipidemias - physiopathology
Immunohistochemistry
Lipoproteins, LDL - metabolism
Low density lipoprotein
Lymph Nodes - cytology
Lymph Nodes - immunology
Male
Mice
Mice, Transgenic
Organ Culture Techniques
Platelet Activating Factor - metabolism
Psoriasis
Receptors, LDL - deficiency
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Skin
Skin - cytology
Skin - immunology
Skin - pathology
Streptococcus infections
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Description
Summary:High LDL and/or low HDL are risk factors for atherosclerosis and are also a common clinical feature in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Here, we show that changes in lipid profiles that reflect atherosclerotic disease led to activation of skin murine dendritic cells (DCs) locally, promoted dermal inflammation, and induced lymph node hypertrophy. Paradoxically, DC migration to lymph nodes was impaired, suppressing immunologic priming. Impaired migration resulted from inhibitory signals generated by platelet-activating factor (PAF) or oxidized LDL that acts as a PAF mimetic. Normal DC migration and priming was restored by HDL or HDL-associated PAF acetylhydrolase (PAFAH), which mediates inactivation of PAF and oxidized LDL. Thus, atherosclerotic changes can sequester activated DCs in the periphery where they may aggravate local inflammation even as they poorly carry out functions that require their migration to lymph nodes. In this context, HDL and PAFAH maintain a normally functional DC compartment.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2004.09.003