Role of Polymorphonuclear Leukocytes in Collar-Induced Intimal Thickening in the Rabbit Carotid Artery

From the Divisions of Pharmacology (D.J.M. Van P., N. Van O., G.R.Y. De M., H.B.) and Immunology (L.S. De C.), University of Antwerp (UIA), Wilrijk; the Division of Physiology (L.J.A.), University of Antwerp (RUCA); and the Department of Pathology, General Hospital Middelheim (M.M.K.), Antwerp, Belgium.

Correspondence to Hidde Bult, University of Antwerp UIA, Division of Pharmacology, Universiteitsplein 1, B-2610 Wilrijk, Belgium. E-mail bult{at}uia.ua.ac.be

Abstract—In this study, the involvement of polymorphonuclear leukocytes (PMNs) in the development of intimal thickening was investigated. A fibromuscular intima was induced by placing a silicone collar around the rabbit carotid artery for 3 days or 2 weeks; the contralateral artery was sham operated. Rabbits received placebo treatments (groups 1 and 3), granulocyte-colony stimulating factor (group 2; G-CSF, 20 µg · kg^-1 · d^-1, delivered by subcutaneous osmotic pumps), or an anti-CD18 monoclonal antibody (group 4; 1.5 mg/kg IV). The G-CSF treatment raised the peripheral PMN count 5- to 12-fold but had no effect on intimal thickening on day 3, 12, or 14. A single injection of anti-CD18 prevented PMN extravasation 6 hours after collar implantation without influencing intimal hyperplasia on day 14. Repeated daily administration of anti-CD18 strongly bound to CD18 on peripheral PMNs and inhibited both PMN-dependent plasma extravasation in the skin and accumulation of CD14-immunoreactive leukocytes in the intima and media. However, anti-CD18 did not suppress early intimal thickening or accumulation of -smooth muscle actin–immunoreactive cells by day 3. It thus appears that the PMN influx in the intima and media evoked by the perivascular collar is of little functional relevance to the subsequent smooth muscle cell migration and intimal thickening in this model.

Key Words: neointima • endothelium • smooth muscle cells • leukocyte adhesion molecules • granulocyte-colony stimulating factor

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