ROLE OF POLYMORPHONUCLEAR LEUKOCYTES IN COLLAR-INDUCED INTIMAL THICKENING IN THE RABBIT CAROTID-ARTERY

In this study, the involvement of polymorphonuclear leukocytes (PMNs) in the development of intimal thickening was investigated. A fibromusc ular intima was induced by placing a silicone collar around the rabbit carotid artery for 3 days or 2 weeks; the contralateral artery was sh am operated. Rabbits received placebo treatments (groups 1 and 3), gra nulocyte-colony stimulating factor (group 2; G-CSF, 20 mu g . kg(-1) . d(-1), delivered by subcutaneous osmotic pumps), or an anti-CD18 mono clonal antibody (group 4; 1.5 mg/kg IV). The G-CSF treatment raised th e peripheral PMN count 5- to 12-fold but had no effect on intimal thic kening on day 3, 12, or 14, A single injection of anti-CD18 prevented PMN extravasation 6 hours after collar implantation without influencin g 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-i mmunoreactive leukocytes in the intima and media. However, anti-CD18 d id not suppress early intimal thickening or accumulation of alpha-smoo th muscle actin-immunoreactive cells by day 3, It thus appears that th e PMN influx in the intima and media evoked by the perivascular collar is of little functional relevance to the subsequent smooth muscle cel l migration and intimal thickening in this model.