Role of leukocytes in neointimal formation after balloon angioplasty in the rabbit atherosclerotic model.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Guzman
L A
LA
Department of Cardiology, Cleveland Clinic Foundation, Ohio, USA.
Forudi
F
F
Villa
A E
AE
Topol
E J
EJ
D000792:Angiography; D000800:Angioplasty, Balloon; D000818:Animals; D000911:Antibodies, Monoclonal; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery / Q000628:therapy; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D003251:Constriction, Pathologic; D007962:Leukocytes / Q000502:physiology*; D011817:Rabbits; D012008:Recurrence; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology*
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens