McFadyen James D, Zeller Johannes, Potempa Lawrence A, Pietersz Geoffrey A, Eisenhardt Steffen U, Peter Karlheinz
Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Department of Medicine, Monash University, Melbourne, VIC, Australia.
Subcell Biochem. 2020;94:499-520. doi: 10.1007/978-3-030-41769-7_20.
C-reactive protein (CRP) is an evolutionary highly conserved member of the pentraxin superfamily of proteins. CRP is widely used as a marker of inflammation, infection and for risk stratification of cardiovascular events. However, there is now a large body of evidence, that continues to evolve, detailing that CRP directly mediates inflammatory reactions and the innate immune response in the context of localised tissue injury. These data support the concept that the pentameric conformation of CRP dissociates into pro-inflammatory CRP isoforms termed pCRP* and monomeric CRP. These pro-inflammatory CRP isoforms undergo conformational changes that facilitate complement binding and immune cell activation and therefore demonstrate the ability to trigger complement activation, activate platelets, monocytes and endothelial cells. The dissociation of pCRP occurs on the surface of necrotic, apoptotic, and ischaemic cells, regular β-sheet structures such as β-amyloid, the membranes of activated cells (e.g., platelets, monocytes, and endothelial cells), and/or the surface of microparticles, the latter by binding to phosphocholine. Therefore, the deposition and localisation of these pro-inflammatory isoforms of CRP have been demonstrated to amplify inflammation and tissue damage in a broad range of clinical conditions including ischaemia/reperfusion injury, Alzheimer's disease, age-related macular degeneration and immune thrombocytopaenia. Given the potentially broad relevance of CRP to disease pathology, the development of inhibitors of CRP remains an area of active investigation, which may pave the way for novel therapeutics for a diverse range of inflammatory diseases.
C反应蛋白（CRP）是五聚体蛋白超家族中进化上高度保守的成员。CRP被广泛用作炎症、感染的标志物以及心血管事件风险分层的指标。然而，现在有大量不断发展的证据详细表明，在局部组织损伤的情况下，CRP直接介导炎症反应和先天免疫反应。这些数据支持这样的概念，即CRP的五聚体构象解离为称为pCRP*的促炎CRP异构体和单体CRP。这些促炎CRP异构体发生构象变化，促进补体结合和免疫细胞活化，因此显示出触发补体激活、激活血小板、单核细胞和内皮细胞的能力。pCRP的解离发生在坏死、凋亡和缺血细胞的表面、规则的β-折叠结构如β-淀粉样蛋白、活化细胞（如血小板、单核细胞和内皮细胞）的膜以及/或微粒的表面，后者通过与磷酸胆碱结合。因此，CRP这些促炎异构体的沉积和定位已被证明在包括缺血/再灌注损伤、阿尔茨海默病、年龄相关性黄斑变性和免疫性血小板减少症在内的广泛临床病症中会放大炎症和组织损伤。鉴于CRP与疾病病理学可能具有广泛的相关性，CRP抑制剂的开发仍然是一个积极研究的领域，这可能为多种炎症性疾病的新型治疗方法铺平道路。
