Role of macrophage scavenger receptors in atherosclerosis
Role of macrophage scavenger receptors in atherosclerosis
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DOI：
10.1016/j.imbio.2012.02.015
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发表时间：
2012-05-01
期刊：
影响因子：
2.8
通讯作者：
Gordon, Siamon
中科院分区：
文献类型：
--
作者：
Kzhyshkowska, Julia;Neyen, Claudine;Gordon, Siamon
越来越多的证据表明动脉粥样硬化是一种慢性炎症性疾病。参与动脉粥样硬化发病机制的关键先天免疫细胞是循环单核细胞和斑块巨噬细胞。免疫和代谢过程之间复杂的相互作用导致这些细胞的病理活动。最容易理解的巨噬细胞介导的病理过程是它们无法正确处理修饰的脂蛋白，导致泡沫细胞的形成，泡沫细胞是动脉粥样硬化斑块的危险成分。参与修饰脂蛋白识别和加工的关键分子是清道夫受体 (SR)。这是一个表面表达的结构异质受体大家族，具有广谱的内源性和外源性配体。 SR 的共同功能特征是细胞外成分的内化并针对它们进行溶酶体降解。然而，这些相对简单的功能可能会产生复杂的后果，因为它们与不同的特定信号传导途径和其他膜转运途径相关。此外，清道夫受体可以与其他类型的受体合作，增加巨噬细胞对多种细胞外配体反应的可变性。至少一些SR通过炎症放大和斑块中巨噬细胞的积累对修饰脂蛋白做出反应，而一些SR可能支持耐受性反应。不同 SR 活动的结果将是单核细胞和巨噬细胞决定保护稳态平衡、通过炎症反应支持动脉粥样硬化进展和斑块不稳定，或支持斑块中稳定斑块的快速纤维化过程。尽管人们对清道夫受体作用的分子机制的了解不断积累，但它们在动脉粥样硬化进展中的作用仍然存在争议。有助于这些过程的清道夫受体的活动是当前审查的主题。 (C) 2012 爱思唯尔有限公司。版权所有。
Accumulating evidence indicates that atherosclerosis is a chronic inflammatory disease. The key innate immune cells that are involved in the pathogenesis of atherosclerosis are circulating monocytes and plaque macrophages. Complex interplay between immune and metabolic processes results in pathological activity of these cells. The best understood pathological process mediated by macrophages is their inability to process modified lipoproteins properly resulting in the formation of foamy cells, which are a dangerous component of atherosclerotic plaques. Key molecules involved in the recognition and processing of modified lipoproteins are scavenger receptors (SR). This is a large family of surface expressed structurally heterogeneous receptors with a broad spectrum of endogenous and exogenous ligands. The common functional feature of SR is internalisation of extracellular components and targeting them for lysosomal degradation. However, these relatively simple functions can have complex consequences, since they are linked to diverse specific signalling pathways and to other membrane transport pathways. Moreover, scavenger receptors can co-operate with other types of receptors increasing the variability of the macrophage response to multiple extracellular ligands. At least some SRs respond to modified lipoproteins by amplification of inflammation and accumulation of macrophages in the plaque, while some SRs may support tolerogenic reactions. Outcome of different SR activities will be the decision of monocytes and macrophage to guard homeostatic balance, support atherosclerosis progression and plaque instability by inflammatory reactions, or support rapid fibrotic processes in the plaque that stabilise it. Despite the accumulating knowledge about the molecular mechanisms of scavenger receptor action, their role in the progression of atherosclerosis remains controversial. The activities of scavenger receptors that can contribute to each of these processes are a subject of current review. (C) 2012 Elsevier GmbH. All rights reserved.