Platelet microparticles - A transcellular delivery system for RANTES promoting monocyte recruitment on endothelium
Platelet microparticles - A transcellular delivery system for RANTES promoting monocyte recruitment on endothelium
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DOI：
10.1161/01.atv.0000170133.43608.37
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发表时间：
2005-07-01
影响因子：
8.7
通讯作者：
Weber, C
中科院分区：
文献类型：
--
作者：
Mause, SF;von Hundelshausen, P;Weber, C
目的：血小板活化介导多种细胞反应，包括RANTES(CCL5)等趋化因子的分泌和血小板微粒(PMPs)的形成。我们研究了PMPs在传递RANTES和促进单核细胞募集方面的作用。方法和结果-在这里，我们发现PMPs含有大量的RANTES，并将RANTES沉积在激活的内皮或小鼠动脉粥样硬化的颈动脉上。流动条件促进了RANTES的沉积，并且比PMP上清液更有效。血流中PMPs与激活的内皮细胞的相互作用主要表现为滚动。RANTES沉积呈现弥散分布模式，很少与牢固附着的PMP共定位，证明RANTES沉积发生在瞬时相互作用中。重要的是，PMPs预灌流可增强激活的内皮或动脉粥样硬化的颈动脉上单核细胞的停滞，这可被阻断抗体或RANTES受体拮抗剂所抑制。P-选择素、糖蛋白Ib(GPIb)、GPIIb/IIIa和连接黏附分子-A对PMP与内皮细胞的相互作用、依赖于PMP的RANTES沉积和随后的单核细胞抑制具有不同的需求。结论循环中的PMPs可能作为RANTES的微调跨细胞递送系统，触发单核细胞对炎症和动脉粥样硬化的内皮细胞的抑制，为炎症和动脉粥样硬化中的血小板依赖单核细胞募集引入了一种新的机制。
Objective-Platelet activation mediates multiple cellular responses, including secretion of chemokines such as RANTES (CCL5), and formation of platelet microparticles (PMPs). We studied the role of PMPs in delivering RANTES and promoting monocyte recruitment.Methods and Results-Here we show that PMPs contain substantial amounts of RANTES and deposit RANTES on activated endothelium or murine atherosclerotic carotid arteries. RANTES deposition is facilitated by flow conditions and more efficient than that conferred by PMP supernatants. Interactions of PMPs with activated endothelium in flow were mostly characterized by rolling. RANTES deposition showed a diffuse distribution pattern and was rarely colocalized with firmly adherent PMPs, substantiating that RANTES deposition occurs during transient interactions. Importantly, preperfusion with PMPs enhanced monocyte arrest on activated endothelium or atherosclerotic carotid arteries, which could be inhibited by a blocking antibody or a RANTES receptor antagonist. Blockade or deficiency of PMP-expressed adhesion receptors demonstrated differential requirement of P-selectin, glycoprotein Ib(GPIb), GPIIb/IIIa, and junctional adhesion molecule-A for PMP interactions with endothelium, PMP-dependent RANTES deposition, and subsequent monocyte arrest.Conclusion-Circulating PMPs may serve as a finely tuned transcellular delivery system for RANTES, triggering monocyte arrest to inflamed and atherosclerotic endothelium, introducing a novel mechanism for platelet-dependent monocyte recruitment in inflammation and atherosclerosis.