Abstract:
:Lipid peroxidation is a common event in health and is greatly accelerated in pro-inflammatory settings such as hypercholesterolemia. Consequently, oxidation-specific epitopes are generated, which are pro-inflammatory and immunogenic, leading to both adaptive and innate responses. Because innate immune mechanisms use conserved germline pattern recognition receptors (PRRs) that are preformed and present at birth, it is not obvious why they should bind to such epitopes. In this review, we put forward the hypothesis that because oxidation-specific epitopes are ubiquitous in both health and disease, and because they in essence represent "danger signals," they constitute a class of pathogen-associated molecular patterns leading to the natural selection of multiple innate PRRs that target such epitopes. We suggest that apoptotic cells, and the blebs and microparticles released from such cells, which are rich in oxidation-specific epitopes and thus pro-inflammatory, constitute an endogenous set of selecting antigens. In turn, natural antibodies, scavenger receptors, and soluble innate proteins, such as pentraxins, all represent PRRs that target such epitopes. We discuss the evidence for this hypothesis and the consequences of such responses in health and disease, such as atherosclerosis.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Hartvigsen K,Chou MY,Hansen LF,Shaw PX,Tsimikas S,Binder CJ,Witztum JLdoi
10.1194/jlr.R800100-JLR200subject
Has Abstractpub_date
2009-04-01 00:00:00pages
S388-93eissn
0022-2275issn
1539-7262pii
R800100-JLR200journal_volume
50 Supplpub_type
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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更新日期:1984-09-01 00:00:00
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