The role of innate immunity in atherogenesis
The role of innate immunity in atherogenesis
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DOI：
10.1194/jlr.r800100-jlr200
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发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Witztum, Joseph L.
中科院分区：
文献类型：
--
作者：
Hartvigsen, Karsten;Chou, Meng-Yun;Witztum, Joseph L.
脂质过氧化在健康中是一种常见的事件，在促炎环境中，如高胆固醇血症，脂质过氧化会大大加速。因此，产生了氧化特异性表位，这些表位是促炎和免疫原性的，导致适应性和先天反应。由于先天免疫机制使用保守的生殖系模式识别受体(PRR)，这些受体在出生时就已经形成并存在，因此它们为什么应该与这些表位结合并不明显。在这篇综述中，我们提出了这样的假设，因为氧化特异性表位在健康和疾病中都是普遍存在的，并且因为它们本质上代表着“危险信号”，它们构成了一类与病原体相关的分子模式，导致了针对这些表位的多个天然PRR的自然选择。我们认为，凋亡细胞及其释放的气泡和微粒富含氧化特异性表位，因此具有促炎作用，构成了一组内源性的选择性抗原。反过来，天然抗体、清道夫受体和可溶性天然蛋白，如五肽，都代表针对这些表位的PRR。我们讨论了这一假设的证据以及这种反应在健康和疾病中的后果，例如动脉粥样硬化。首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容天然免疫在动脉粥样硬化形成中的作用。J.Lipid Res.2009年。S388-S393。
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.-Hartvigsen, K., M-Y. Chou, L. F. Hansen, P. X. Shaw, S. Tsimikas, C. J. Binder, and J. L. Witztum. The role of innate immunity in atherogenesis. J. Lipid Res. 2009. S388-S393.