Objective-Thrombotic events and immunoinflammatory processes take place next to each other during vascular remodeling in atherosclerotic lesions. In this study we investigated the interaction of platelets with dendritic cells (DCs). Methods and Results-The rolling of DCs on platelets was mediated by PSGL-1. Firm adhesion of DCs was mediated through integrin ␣ M  2 (Mac-1). In vivo, adhesion of DCs to injured carotid arteries in mice was mediated by platelets. Pretreatment with soluble GPVI, which inhibits platelet adhesion to collagen, substantially reduced recruitment of DCs to the injured vessel wall. In addition, preincubation of DCs with sJAM-C significantly reduced their adhesion to platelets. Coincubation of DCs with platelets induced maturation of DCs, as shown by enhanced expression of CD83. In the presence of platelets, DC-induced lymphocyte proliferation was significantly enhanced. Moreover, coincubation of DCs with platelets resulted in platelet phagocytosis by DCs, as verified by different cell phagocytosis assays. Finally, platelet/DC interaction resulted in apoptosis of DCs mediated by a JAM-Cdependent mechanism. Conclusions-Recruitment of DCs by platelets, which is mediated via CD11b/CD18 (Mac-1) and platelet JAM-C, leads to DC activation and platelet phagocytosis. This process may be of importance for progression of atherosclerotic lesions. 3 In atherosclerotic plaques, the number of DCs is substantially enhanced and DCs preferentially accumulate at rupture-prone regions. 4,5 Recently, DCs were shown to accumulate in the intima of atherosclerosis-predisposed regions of the aorta of C57BL/6 mice. 6 However, the mechanisms involved in the recruitment of circulating DCs at site of vascular lesions are poorly understood so far.It is well recognized that platelets rapidly adhere to the extracellular matrix of the subendothelium at sites of vascular lesions. If this process is controlled, platelets passivate vascular injury and initiate the healing process. 1 However, uncontrolled platelet-mediated thrombus formation leads to acute thrombotic occlusion or plaque progression resulting in, eg, acute coronary syndrome. 7 Platelet-mediated cell recruitment to the atherosclerotic plaque plays a central role for vascular repair mechanisms. DCs participate both in the innate and adaptive immune system and represent highly specialized antigen-presenting cells. 8 Thereby, they are capable of stimulating naive, memory, and effector T-cells, as well as activating natural killer cells. 8 Proteins are internalized by phagocytosis, degraded into short peptides, and presented via the MHC II receptors. 9 During maturation, DCs express various adhesion receptors, which enable DCs to interact with other cell types and mediate homing of DCs to target tissues. 4,8 Original The present study evaluates the role of platelets for DC adhesion to vascular lesions and shows that platelets play a critical role for the recruitment and function of DCs. Materials and MethodsDCs were generated from buffy coats derived fr...
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