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调节细胞黏附的整合素蛋白CD11b与其配体ICAM-1的相互作用在动脉粥样硬化的炎症进程中起至关重要的作用.阿托伐他汀(Atorvastatin,ATV)作为他汀类药物中的主要成员,以其良好的降脂作用广泛应用于动脉粥样硬化疾病的临床治疗,同时大量证据表明ATV还具有独立的抗炎作用,但其具体分子机制尚未完全明确.我们应用活细胞单分子力谱法研究了ATV干预对ICAM-1/CD11b相互作用的影响.结果表明原子力显微镜(AFM)在活细胞表面测得单对黏附分子ICAM-1/CD11b的相互作用力值约为40pN,ATV不能通过直接阻断ICAM-1或CD11b影响其单分子黏附力,而抗ICAM-1单克隆抗体则有效降低了此对黏附分子作用力.此外,流式结果表明ATV干预有效抑制了肿瘤坏死因子(TNF-α)诱导的人脐静脉内皮细胞(HUVEC)表面ICAM-1表达增加.本研究建立的方法模型可作为活细胞体系研究临床药物影响细胞黏附分子间相互作用及抗炎机制的重要手段.
Interaction of integrin CD11b, a regulator of cellular adhesion, with its ligand ICAM-1 plays a crucial role in the inflammatory process of atherosclerosis.Atorvastatin (ATV), as a major member of statins, , With its good lipid-lowering effect widely used in the clinical treatment of atherosclerotic disease, while a large number of evidence that ATV also has an independent anti-inflammatory effect, but its specific molecular mechanism is not yet fully clear.We use the single cell molecular weight spectrum Method was used to study the effect of ATV intervention on the interaction of ICAM-1 / CD11b. The results showed that the interaction force of ICAM-1 / CD11b on the surface of living cells was about 40pN and the ATV could not pass the AFM ICAM-1 or CD11b directly blocked its single-molecule adhesion, while anti-ICAM-1 monoclonal antibody effectively reduced the binding force of the adhesion molecules.In addition, flow cytometry results showed that ATV intervention effectively inhibited tumor necrosis factor (TNF) -α) -induced ICAM-1 expression on the surface of human umbilical vein endothelial cells (HUVECs) .Methods The model established in this study can be used as a living cell system to study the effect of clinical drugs on the interaction of cell adhesion molecules And an important means of anti-inflammatory mechanisms.