Gawaz M, Neumann F J, Dickfeld T, Koch W, Laugwitz K L, Adelsberger H, Langenbrink K, Page S, Neumeier D, Schömig A, Brand K
Medizinische Klinik und Deutsches Herzzentrum and Institut für klinische Chemie und Pathobiologie, Klinikum rechts der Isar der Technischen Universität München, Germany.
Circulation. 1998 Sep 22;98(12):1164-71. doi: 10.1161/01.cir.98.12.1164.
Platelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis. The role of platelets for monocyte chemotactic protein-1 (MCP-1) secretion and surface expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells has been assessed.
Monolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours, and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry, respectively. In the presence of ADP-activated platelets, both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets (P<0.02). Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) determined by electrophoretic mobility shift assay and kappaB-dependent transcriptional activity was enhanced in the presence of activated platelets. In addition, ADP-activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription. Liposomal transfection of a double-stranded kappaB phosphorothioate oligonucleotide, but not of the mutated form, inhibited MCP-1 secretion and surface expression of ICAM-1 on activated endothelium (P<0.05).
The present study indicates that activated platelets modulate chemotactic (MCP-1) and adhesive (ICAM-1) properties of endothelial cells via an NF-kappaB-dependent mechanism. Platelet-induced activation of the NF-kappaB system might contribute to early inflammatory events in atherogenesis.
血小板/内皮细胞相互作用在炎症和动脉粥样硬化的病理生理学中起重要作用。已评估血小板对单核细胞趋化蛋白-1（MCP-1）分泌及内皮细胞上细胞间黏附分子-1（ICAM-1）表面表达的作用。
将人脐静脉内皮细胞单层与未刺激或ADP激活的血小板孵育6小时，分别通过酶联免疫吸附测定（ELISA）和流式细胞术测定MCP-1的分泌及ICAM-1的表面表达。与未刺激的血小板相比，在存在ADP激活的血小板时，MCP-1分泌和ICAM-1表面表达均显著增加（P<0.02）。通过电泳迁移率变动分析测定的转录因子核因子-κB（NF-κB）的激活及κB依赖性转录活性在存在激活的血小板时增强。此外，ADP激活的血小板诱导MCP-1和ICAM-1启动子依赖性转录。脂质体转染双链κB硫代磷酸酯寡核苷酸而非其突变形式可抑制激活的内皮细胞上MCP-1的分泌及ICAM-1的表面表达（P<0.05）。
本研究表明激活的血小板通过NF-κB依赖性机制调节内皮细胞的趋化（MCP-1）和黏附（ICAM-1）特性。血小板诱导的NF-κB系统激活可能有助于动脉粥样硬化形成过程中的早期炎症事件。
