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

Abstract

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, 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. (Arterioscler Thromb Vasc Biol. 1998;18:915-921.)

Monoclonal Antibody Against Vascular Cell Adhesion Molecule-1 Inhibits Neointimal Formation After Periadventitial Carotid Artery Injury in Genetically Hypercholesterolemic Mice

“…25 In a cuff model with electrical stimulusinduced injury, mononuclear cell but not polymorphonuclear influx was shown to influence intimal thickening. 10 Although the present study was not designed to determine specific cell infiltrates, on the basis of previous results outlined above, 10,24 it is reasonable to speculate that polymorphonuclear influx does not significantly affect intimal thickening in the cuffinjury model. In the present report, the reduction of neointimal formation with antibody treatment was associated with reduced inflammatory infiltrates, suggesting further that monocyte/macrophage accumulation plays a role in promoting neointimal formation in injured arteries of apoE KO mice.…”

“…A rabbit cuff-injury model using antibody blockade of leukocytes showed that polymorphonuclear influx had little effect on SMC migration and intimal thickening. 24 It is notable that mononuclear cells were present in significant quantity only after prolonged exposure of the artery to LDL in vivo. This exposure to LDL also significantly increased intimal thickening.…”

Assessment of Myeloperoxidase Activity by the Conversion of Hydroethidine to 2-Chloroethidium

“…As a second model of inflammation, we applied a non-occlusive cuff to the femoral artery, known to cause acute and then sustained vascular inflammation characterized by arterial infiltration of predominantly PMN (29,42,43). Indeed, within 24 h large numbers of inflammatory cells infiltrated the left femoral artery around which a cuff was placed, and leukocytes remained present in the "cuffed" artery for up to 14 days (Fig.…”

Targeting CCR2 or CD18 Inhibits Experimental In-Stent Restenosis in Primates

“…In contrast, Golino et al 23 reported that administration of a mAb against CD18 (R15.7) in a rabbit carotid model of injury involving placement of a constrictor around the vessel produced significant inhibition of neointimal hyperplasia. Van Put et al 24 also studied the effect of a mAb against CD18 (R15.7) in a collar-induced injury model in rabbit iliac arteries. They found plentiful neutrophils and small numbers of monocytes (CD14 positive cells) after injury.…”