Takemoto Y, Matsuda T, Kishimoto T, Maekawa M, Akutsu T
Department of Bioengineering, National Cardiovascular Center Research Institute, Osaka, Japan.
ASAIO Trans. 1989 Jul-Sep;35(3):354-6. doi: 10.1097/00002480-198907000-00059.
This study was conducted to clarify cellular adhesion mechanisms of blood cells (platelets [PLT] and white blood cells [WBC]) and vascular endothelial cells at the molecular level. This study indicated that the adhesion of three cellular systems to proteins such as fibronectin and fibrinogen proceeds via the RGD (Arg-Gly-Asp) ligand-receptor interaction, in which the RGD tripeptidyl sequence is the minimal amino acid sequence common to adhesive proteins. This was evident from the dose-dependent inhibitory effect of RGD-containing peptide on cellular adhesion. Additional supporting evidence was the presence of PLT and WBC receptors, which molecularly recognize RGD, verified by fluorescein-labelled RGD-containing peptide. The adhesion of vascular endothelial cells was also predominantly controlled by the ligand-receptor mechanism, and participation of complement activation on WBC adhesion was demonstrated as well. The adhesion of WBCs on surface hydroxyl group-bearing polymers proceeded via the CR3 receptor-C3b ligand interaction, in which activated complement factor C3b is chemically fixed upon complement activation. Thus, the molecular understanding of cellular adhesion mechanisms provide the basis of biocompatibility for implantation and extracorporeal circulation, as well as molecular design of artificial and bioartificial organs.
本研究旨在从分子水平阐明血细胞（血小板[PLT]和白细胞[WBC]）与血管内皮细胞的细胞黏附机制。本研究表明，三种细胞系统与纤连蛋白和纤维蛋白原等蛋白质的黏附是通过RGD（精氨酸-甘氨酸-天冬氨酸）配体-受体相互作用进行的，其中RGD三肽序列是黏附蛋白共有的最小氨基酸序列。含RGD肽对细胞黏附的剂量依赖性抑制作用证明了这一点。额外的支持证据是通过荧光素标记的含RGD肽验证的血小板和白细胞受体的存在，这些受体能分子识别RGD。血管内皮细胞的黏附也主要受配体-受体机制控制，同时也证明了补体激活参与白细胞黏附。白细胞在含表面羟基聚合物上的黏附是通过CR3受体-C3b配体相互作用进行的，其中活化的补体因子C3b在补体激活后化学固定。因此，对细胞黏附机制的分子理解为植入和体外循环的生物相容性以及人工和生物人工器官的分子设计提供了基础。
