Flierl Ulrike, Bauersachs Johann, Schäfer Andreas
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Eur J Clin Invest. 2015 Jun;45(6):624-33. doi: 10.1111/eci.12443. Epub 2015 Apr 24.
The chemokine fractalkine, CX3CL1, bears unique features within the chemokine family: it exists in a membrane bound form acting as an adhesion molecule and surface receptor; however, when cleaved by ADAM 10, it functions as a soluble chemokine. Fractalkine and its chemokine receptor CX3CR1 are known to have multiple roles in diverse human diseases, for example inflammatory diseases, rheumatoid arthritis, renal diseases and atherosclerosis.
This review is based on the material obtained via PubMed up to November 2014. The key search terms used were 'fractalkine', 'CX3CL1', 'CX3CR1', 'cardiovascular disease', 'platelets', 'monocytes' and 'platelet-monocyte complexes'.
Atherosclerosis is recognized as a highly inflammatory disease, and it has become increasingly evident that the immune system plays an important role in atherogenesis and atheroprogression. Two blood cell populations are crucially involved in the early development of atherosclerotic lesions: monocytes and platelets. They are detected at vascular sites of endothelial dysfunction and are involved in inflammatory immune responses. These cells directly interact with each other, forming platelet-monocyte complexes that are increased in cardiovascular diseases. During the development of atherosclerosis, fractalkine mediates leukocyte recruitment to the inflamed endothelium, which promotes early formation of lesions. This process only effectively works in the presence of activated platelets. It has been suggested that fractalkine and its receptor contribute to platelet-monocyte aggregate formation underlining the two important impacts of this chemokine for platelets as well as monocytes.
Interesting data hint at a role of fractalkine for platelet activation, adhesion and subsequent monocyte recruitment to activated endothelial cells in cardiovascular diseases. However, the exact mechanisms remain to become unravelled.
趋化因子fractalkine（CX3CL1）在趋化因子家族中具有独特特征：它以膜结合形式存在，作为一种黏附分子和表面受体；然而，当被ADAM 10裂解后，它发挥可溶性趋化因子的功能。已知fractalkine及其趋化因子受体CX3CR1在多种人类疾病中具有多种作用，例如炎症性疾病、类风湿性关节炎、肾脏疾病和动脉粥样硬化。
本综述基于截至2014年11月通过PubMed获得的资料。使用的关键检索词为“fractalkine”“CX3CL1”“CX3CR1”“心血管疾病”“血小板”“单核细胞”和“血小板 - 单核细胞复合物”。
动脉粥样硬化被认为是一种高度炎症性疾病，并且越来越明显的是免疫系统在动脉粥样硬化的发生和发展中起重要作用。两种血细胞群体在动脉粥样硬化病变的早期发展中至关重要：单核细胞和血小板。它们在内皮功能障碍的血管部位被检测到，并参与炎症免疫反应。这些细胞直接相互作用，形成在心血管疾病中增加的血小板 - 单核细胞复合物。在动脉粥样硬化的发展过程中，fractalkine介导白细胞募集到炎症内皮，这促进了病变的早期形成。这个过程仅在活化血小板存在的情况下有效发挥作用。有人提出fractalkine及其受体有助于血小板 - 单核细胞聚集体的形成，突出了这种趋化因子对血小板以及单核细胞的两个重要影响。
有趣的数据表明fractalkine在心血管疾病中对血小板活化、黏附以及随后单核细胞募集到活化内皮细胞方面发挥作用。然而，确切机制仍有待阐明。
