ROLE OF LEUKOCYTES IN NEOINTIMAL FORMATION AFTER BALLOON ANGIOPLASTY IN THE RABBIT ATHEROSCLEROTIC MODEL

Background: Adherence and transendothelial migration of circulating le ukocytes is one of the initial events after vascular injury. This proc ess is mediated principally by the expression of integrins (CD11/C18) on the cell surface, which interact with their counterparts in the ves sel wall cells. In order to determine the role of leukocytes in the de velopment of neointimal thickening after balloon angioplasty, a monocl onal antibody (R15.7) against leukocyte adherence glycoprotein CD18 wa s used. Methods: Femoral artery atherosclerotic lesions were induced i n 20 New Zealand White rabbits, which were subjected to balloon angiop lasty 28 days thereafter. Twelve hours before and 48 h after balloon a ngioplasty, 2 mg/kg body weight anti-CD18 or vehicle was randomly inje cted 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 ser um sample to inhibit aggregation of JY cells. Results: The serum obtai ned from monoclonal antibody-treated rabbits showed more than 50% inhi bition of cell aggregation at the time of balloon angioplasty. No effe ct on cell aggregation was seen in the sera of control rabbits. By ang iography, there was no difference in lumen diameter and percentage ste nosis at follow-up between the two groups. On morphometric analysis, t here were no differences in the cross-sectional areas of intima, media , and lumen between the two treatment groups. The percentage cross-sec tional area of intima was also similar in the two groups (0.672+/-0.04 versus 0.628+/-0.04). Conclusions: Blocking the CD18/CD11 glycoprotei n pathway for leukocyte adhesion with a specific monoclonal antibody d id not decrease the restenotic process after balloon angioplasty in th e atherosclerotic rabbit arterial injury model.