Endothelial cell-borne platelet bridges selectively recruit monocytes in human and mouse models of vascular inflammation
Endothelial cell-borne platelet bridges selectively recruit monocytes in human and mouse models of vascular inflammation
复制标题
DOI：
10.1093/cvr/cvr040
复制
发表时间：
2011-07-01
影响因子：
10.8
通讯作者：
Rainger, George Ed
中科院分区：
文献类型：
--
作者：
Kuckleburg, Christopher J.;Yates, Clara M.;Rainger, George Ed
单核细胞系细胞是动脉粥样硬化病变中最丰富的炎性细胞。单核细胞的炎性浸润的优势表明存在支持其选择性募集的疾病驱动机制。以往的研究表明，内皮细胞（EC）和血小板之间的相互作用可能会促进单核细胞的募集。在这项研究中，我们试图扩大这方面的知识，使用一个复杂的共培养模型的患病vessel wall.Methods和结果使用原代人类细胞在体外流动为基础的粘附试验，我们发现，分泌性动脉平滑肌细胞（SMCs），共培养的内皮细胞，促进优先招聘的单核细胞从血液中的TGF-β 1依赖的方式。约85%募集至内皮的白细胞为CD（14+）。内皮细胞上粘附性血小板桥的形成对于单核细胞募集是必不可少的，因为去除血小板或抑制粘附于内皮细胞会消除单核细胞募集。通过血小板P-选择素从流动中募集单核细胞并通过EC衍生的CC趋化因子配体2（CCL 2）活化，尽管CCL 2向粘附单核细胞的呈递依赖于血小板活化和CXC趋化因子配体4（CXCL 4）的释放。在小鼠体内TGF-β 1驱动的血管炎症模型中，血小板也是有效的白细胞募集到提睾肌微循环血管所必需的。结论在这项研究中，我们已经证明，在患病动脉壁内发现的基质细胞可能促进单核细胞的优先募集，这是通过建立SMC，EC，血小板，和单核细胞。
Aims Cells of the monocyte lineage are the most abundant inflammatory cells found in atherosclerotic lesions. Dominance of the inflammatory infiltrate by monocytes indicates that there is a disease-driven mechanism supporting their selective recruitment. Previous studies have demonstrated that interactions between endothelial cells (ECs) and platelets may promote monocyte recruitment. In this study, we sought to expand on this knowledge using a complex coculture model of the diseased vessel wall.Methods and results Using primary human cells in an in vitro flow-based adhesion assay, we found that secretory arterial smooth muscle cells (SMCs), cocultured with ECs, promote preferential recruitment of monocytes from blood in a TGF-beta 1-dependent manner. Approximately 85% of leucocytes recruited to the endothelium were CD(14+). Formation of adhesive platelet bridges on ECs was essential for monocyte recruitment as platelet removal or inhibition of adhesion to the ECs abolished monocyte recruitment. Monocytes were recruited from flow by platelet P-selectin and activated by EC-derived CC chemokine ligand 2 (CCL2), although the presentation of CCL2 to adherent monocytes was dependent upon platelet activation and release of CXC chemokine ligand 4 (CXCL4). In an intravital model of TGF-beta 1-driven vascular inflammation in mice, platelets were also necessary for efficient leucocyte recruitment to vessels of the microcirculation in the cremaster muscle.Conclusions In this study, we have demonstrated that stromal cells found within the diseased artery wall may promote the preferential recruitment of monocytes and this is achieved by establishing a cascade of interactions between SMCs, ECs, platelets, and monocytes.