【摘要】 已有的研究结果表明,肝素可以作为β2-整合素(Mac-1)的配体抑制炎症过程中Mac-1介导的嗜中性粒细胞与血管内皮细胞的黏附.通过选择性化学修饰方法制备了具有低抗凝血活性的高碘酸氧化-硼氢化钠还原肝素(RO-肝素),系统地研究了它对Mac-1介导的嗜中性粒细胞黏附的抑制作用.结果表明,显著失去抗凝血活性的RO-肝素仍能有效地抑制Mac-1介导的嗜中性粒细胞与ICAM-1重组蛋白、转染ICAM-1 cDNA的COS-7细胞和人脐静脉内皮细胞黏附.为深入阐明拮抗Mac-1介导的白细胞黏附的分子机制和筛选抗炎症药物提供了有价值的实验证据.更多还原

【Abstract】 The adhesion of leukocytes to vascular endothelium is crucial for the generation of inflammatory responses. The selectins and β2-integrin (Mac-1) play a major role in the process. Recently, it was reported that RO-heparin can inhibit selectin-mediated leukocyte adhesion. The effect of RO-heparin on the Mac-1-mediated neutrophils adhesion were further tested. The results showed that RO-heparin could effectively inhibit neutrophils binding to ICAM-1, adhering to COS-7 cells expressing human ICAM-1, and adhering to human umbilical vein endothelial cells (HUVECs) under static and flow conditions. The findings suggest that the effect of RO-heparin on leukocyte adhesion is mainly due to its inhibition on the interaction between selectins or Mac-1 and their ligands and that RO-heparin might be useful in preventing inflammation diseases.更多还原