Guzman L A, Forudi F, Villa A E, Topol E J
Department of Cardiology, Cleveland Clinic Foundation, Ohio, USA.
Coron Artery Dis. 1995 Sep;6(9):693-701.
Adherence and transendothelial migration of circulating leukocytes is one of the initial events after vascular injury. This process is mediated principally by the expression of integrins (CD11/C18) on the cell surface, which interact with their counterparts in the vessel wall cells. In order to determine the role of leukocytes in the development of neointimal thickening after balloon angioplasty, a monoclonal antibody (R15.7) against leukocyte adherence glycoprotein CD18 was used.
Femoral artery atherosclerotic lesions were induced in 20 New Zealand White rabbits, which were subjected to balloon angioplasty 28 days thereafter. Twelve hours before and 48 h after balloon angioplasty, 2 mg/kg body weight anti-CD18 or vehicle was randomly injected intravenously. Twenty-one days later the rabbits were killed and morphometric analysis performed. Measurement of functional activity of R15.7 in rabbit sera was performed, analyzing the capacity of the serum sample to inhibit aggregation of JY cells.
The serum obtained from monoclonal antibody-treated rabbits showed more than 50% inhibition of cell aggregation at the time of balloon angioplasty. No effect on cell aggregation was seen in the sera of control rabbits. By angiography, there was no difference in lumen diameter and percentage stenosis at follow-up between the two groups. On morphometric analysis, there were no differences in the cross-sectional areas of intima, media, and lumen between the two treatment groups. The percentage cross-sectional area of intima was also similar in the two groups (0.672 +/- 0.04 versus 0.628 +/- 0.04).
Blocking the CD18/CD11 glycoprotein pathway for leukocyte adhesion with a specific monoclonal antibody did not decrease the restenotic process after balloon angioplasty in the atherosclerotic rabbit arterial injury model.
循环白细胞的黏附和跨内皮迁移是血管损伤后的初始事件之一。这一过程主要由细胞表面整合素（CD11/C18）的表达介导，整合素与血管壁细胞中的对应物相互作用。为了确定白细胞在球囊血管成形术后新生内膜增厚发展中的作用，使用了一种针对白细胞黏附糖蛋白CD18的单克隆抗体（R15.7）。
在20只新西兰白兔中诱导股动脉粥样硬化病变，28天后对其进行球囊血管成形术。在球囊血管成形术前12小时和术后48小时，将2mg/kg体重的抗CD18或赋形剂随机静脉注射。21天后处死兔子并进行形态计量分析。对兔血清中R15.7的功能活性进行测量，分析血清样本抑制JY细胞聚集的能力。
在球囊血管成形术时，从单克隆抗体处理的兔子获得的血清显示细胞聚集抑制率超过50%。在对照兔的血清中未观察到对细胞聚集的影响。通过血管造影，两组随访时管腔直径和狭窄百分比无差异。形态计量分析显示，两个治疗组的内膜、中膜和管腔横截面积无差异。两组内膜的横截面积百分比也相似（0.672±0.04对0.628±0.04）。
在动脉粥样硬化兔动脉损伤模型中，用特异性单克隆抗体阻断CD18/CD11糖蛋白途径以阻止白细胞黏附，并未降低球囊血管成形术后的再狭窄过程。
