Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. / Miller, Yury I; Choi, Soo-Ho; Wiesner, Philipp; Fang, Longhou; Harkewicz, Richard; Hartvigsen, Karsten; Boullier, Agnès; Gonen, Ayelet; Diehl, Cody J; Que, Xuchu; Montano, Erica; Shaw, Peter X; Tsimikas, Sotirios; Binder, Christoph J; Witztum, Joseph L.
I: Circulation Research, Bind 108, Nr. 2, 2011, s. 235-48.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity
AU - Miller, Yury I
AU - Choi, Soo-Ho
AU - Wiesner, Philipp
AU - Fang, Longhou
AU - Harkewicz, Richard
AU - Hartvigsen, Karsten
AU - Boullier, Agnès
AU - Gonen, Ayelet
AU - Diehl, Cody J
AU - Que, Xuchu
AU - Montano, Erica
AU - Shaw, Peter X
AU - Tsimikas, Sotirios
AU - Binder, Christoph J
AU - Witztum, Joseph L
PY - 2011
Y1 - 2011
N2 - Oxidation reactions are vital parts of metabolism and signal transduction. However, they also produce reactive oxygen species, which damage lipids, proteins and DNA, generating "oxidation-specific" epitopes. In this review, we discuss the hypothesis that such common oxidation-specific epitopes are a major target of innate immunity, recognized by a variety of "pattern recognition receptors" (PRRs). By analogy with microbial "pathogen-associated molecular patterns" (PAMPs), we postulate that host-derived, oxidation-specific epitopes can be considered to represent "danger (or damage)-associated molecular patterns" (DAMPs). We also argue that oxidation-specific epitopes present on apoptotic cells and their cellular debris provided the primary evolutionary pressure for the selection of such PRRs. Furthermore, because many PAMPs on microbes share molecular identity and/or mimicry with oxidation-specific epitopes, such PAMPs provide a strong secondary selecting pressure for the same set of oxidation-specific PRRs as well. Because lipid peroxidation is ubiquitous and a major component of the inflammatory state associated with atherosclerosis, the understanding that oxidation-specific epitopes are DAMPs, and thus the target of multiple arcs of innate immunity, provides novel insights into the pathogenesis of atherosclerosis. As examples, we show that both cellular and soluble PRRs, such as CD36, toll-like receptor-4, natural antibodies, and C-reactive protein recognize common oxidation-specific DAMPs, such as oxidized phospholipids and oxidized cholesteryl esters, and mediate a variety of immune responses, from expression of proinflammatory genes to excessive intracellular lipoprotein accumulation to atheroprotective humoral immunity. These insights may lead to improved understanding of inflammation and atherogenesis and suggest new approaches to diagnosis and therapy.
AB - Oxidation reactions are vital parts of metabolism and signal transduction. However, they also produce reactive oxygen species, which damage lipids, proteins and DNA, generating "oxidation-specific" epitopes. In this review, we discuss the hypothesis that such common oxidation-specific epitopes are a major target of innate immunity, recognized by a variety of "pattern recognition receptors" (PRRs). By analogy with microbial "pathogen-associated molecular patterns" (PAMPs), we postulate that host-derived, oxidation-specific epitopes can be considered to represent "danger (or damage)-associated molecular patterns" (DAMPs). We also argue that oxidation-specific epitopes present on apoptotic cells and their cellular debris provided the primary evolutionary pressure for the selection of such PRRs. Furthermore, because many PAMPs on microbes share molecular identity and/or mimicry with oxidation-specific epitopes, such PAMPs provide a strong secondary selecting pressure for the same set of oxidation-specific PRRs as well. Because lipid peroxidation is ubiquitous and a major component of the inflammatory state associated with atherosclerosis, the understanding that oxidation-specific epitopes are DAMPs, and thus the target of multiple arcs of innate immunity, provides novel insights into the pathogenesis of atherosclerosis. As examples, we show that both cellular and soluble PRRs, such as CD36, toll-like receptor-4, natural antibodies, and C-reactive protein recognize common oxidation-specific DAMPs, such as oxidized phospholipids and oxidized cholesteryl esters, and mediate a variety of immune responses, from expression of proinflammatory genes to excessive intracellular lipoprotein accumulation to atheroprotective humoral immunity. These insights may lead to improved understanding of inflammation and atherogenesis and suggest new approaches to diagnosis and therapy.
KW - Animals
KW - Atherosclerosis
KW - Epitopes
KW - Humans
KW - Immunity, Innate
KW - Oxidation-Reduction
KW - Oxidative Phosphorylation
KW - Receptors, Pattern Recognition
U2 - 10.1161/CIRCRESAHA.110.223875
DO - 10.1161/CIRCRESAHA.110.223875
M3 - Journal article
C2 - 21252151
VL - 108
SP - 235
EP - 248
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 2
ER -
ID: 40254843