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Oxidation-specific ...
Oxidation-specific epitopes are important targets of innate immunity.
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Chou, M-Y (författare)
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Hartvigsen, K (författare)
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Hansen, L F (författare)
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- Fogelstrand, Linda, 1974 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Shaw, P X (författare)
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Boullier, A (författare)
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Binder, C J (författare)
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Witztum, J L (författare)
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(creator_code:org_t)
- Wiley, 2008
- 2008
- Engelska.
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Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 263:5, s. 479-88
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- During the oxidation of LDL, a central pathophysiological component of atherogenesis, a wide variety of chemical and physical changes occur leading to the generation of oxidation-specific neoepitopes. These epitopes are not only immunogenic, leading to adaptive humoral responses, but are also a prominent target of multiple arcs of innate immunity. The pattern recognition receptors (PRRs) of innate immunity are germ line encoded, conserved by natural selection, and bind to pathogen-associated molecular patterns (PAMPs) common on multiple structures. However, it is not intuitive as to why they should recognize oxidation-specific neoepitopes. Yet it is clear that multiple macrophage scavenger receptors, which are classic PRRs, recognize oxidation-specific epitopes, such as those found on oxidized LDL (OxLDL). Other innate proteins, such as C-reactive protein, also bind to OxLDL. Natural antibodies (NAbs), the humoral arc of innate immunity, provide a nonredundant role in the first line of defence against pathogens, but are also believed to provide important homeostatic house-keeping functions against self-antigens. Our work demonstrates that oxidation-specific epitopes, as found on OxLDL, are a major target of NAbs. In this review, we will discuss the specific example of the prototypic NAb T15/E06, which is increased in atherosclerotic mice and mediates atheroprotection, and discuss the potential role of NAbs in atherogenesis, and in inflammation in general. We also review data that oxidation-specific epitopes are generated whenever cells undergo programmed cell death, forming a common set of PAMPs recognized by oxidation-specific PRRs on macrophages, NAbs and innate proteins. We present the hypothesis that oxidation-specific epitopes on apoptotic cells exerted evolutionary pressure for the conservation of these PRRs and also serve to maintain the expansion of a substantial proportion of NAbs directed to these stress-induced self-antigens.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
Nyckelord
- Animals
- Apoptosis
- physiology
- Atherosclerosis
- immunology
- physiopathology
- B-Lymphocytes
- immunology
- Epitopes
- biosynthesis
- immunology
- Immunity
- Innate
- immunology
- Immunoglobulin M
- immunology
- Lipoproteins
- LDL
- Mice
- Rabbits
- Receptors
- Pattern Recognition
Publikations- och innehållstyp
- ref (ämneskategori)
- for (ämneskategori)
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