Rolling and adhesion of monocytes to early atherosclerotic lesions of apolipoprotein E-/-(apoE-/-) mice requires P-selectin, PSGL-1, /spl alpha//sub 4/ integrin and VCAM-1

To investigate the molecular basis of mononuclear cell rolling and adhesions to vascular endothelium prone to develop atherosclerotic lesion, isolated carotid arteries from ApoE-/- and other relevant mice were perfused under physiological shear stress conditions. Carotid arteries from 10-12 weeks old ApoE-/- and C57BL/6 wide-type mice fed a Western diet for 4-5 weeks, representing early atherosclerotic lesions according to vessel histology, supported mononuclear cell (U937) attachment, rolling and adhesion, while carotid arteries from an atherosclerosis-resistant strain (BALB/C) showed no adhesion. Antibody blocking assays showed that mononuclear rolling and adhesion were significantly inhibited by treating the vessel with P-selectin antibody or treating U937 with anti-PSGL-1. Treating the vessel with VCAM-1 antibody or treating U937 with /spl alpha//sub 4//spl beta//sub 1/ integrin antibody caused rolling velocities to increase (from 86/spl plusmn/4 to 167/spl plusmn/7 /spl mu/m/s). This suggests that mononuclear cell can attach, roll and adhere on early atherosclerotic endothelium via the P-selectin-PSGL-1 and VCAM-1-/spl alpha//sub 4//spl beta//sub 1/ pathways.