Oxidation-Specific Epitopes are Danger Associated Molecular Patterns Recognized by Pattern Recognition Receptors of Innate Immunity

By Yury I. Miller, Soo-Ho Choi, Philipp Wiesner, Longhou Fang, R. Harkewicz, K. Hartvigsen, A. Boullier, A. Gonen, Cody J. Diehl, X. Que and 5 more. Circulation Research, 2011

641 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/07efad3aebad8a01d1913fd6eefdeb187e4fd6f9

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Citations in the corpus

Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans (2013, background): “Impaired clearance of such apoptotic debris (impaired efferocytosis) may thus contribute to growth and thrombotic complications of atherosclerotic lesions (Moore and Tabas, 2011).”
Immunity, atherosclerosis and cardiovascular disease (2013, background): “Modified and oxidized apolipoprotein B (apoB) and cholesterol could also be implicated [17] although”
The role of oxidative stress during inflammatory processes (2013, background): “Evidence accumulated over the past two decades has pointed to significant connections between inflammation and oxidative stress, both processes contributing to fuel the other one, thereby establishing a vicious cycle able to perpetuate and propagate the inflammatory response.”
Immunogenic cell death and DAMPs in cancer therapy (2012, background): “These authors showed that a recombinant N-terminal fragment of CRT (39-272) is a potent inducer of activation and maturation of B cells and macrophages and can trigger Ig class switching in B cells without T cell help in vitro and in vivo72.”
Cytokines in Radiobiological Responses: A Review (2012, positive): “oxidation-specific moieties a particularly interesting source of DAMPS in response to radiation (72).”
Inflammation and atherosclerosis: signaling pathways and therapeutic intervention (2022, background): “Much evidence suggests that potential major antigens involved in atherosclerosis include neoepitopes generated by oxidized LDL (oxLDL) formed in the vessel wall or when cells undergo apoptotic death.(9) In addition, other potential antigens released from apoptotic cells in the plaques can further pr”