Population of the Vessel Wall by Leukocytes Binding to P-Selectin in a Model of Disturbed Arterial Flow

Abstract

We examined the hypothesis that disturbance of laminar flow promotes the attachment of leukocytes to the vessel wall in regions where the wall shear stress is otherwise too high. Isolated neutrophils, lymphocytes, or monocytes were perfused through chambers with backward-facing steps so that vortices occurred with well-defined reattachment of flow. Wall shear stresses downstream in reestablished flow equaled 0.07 Pa (low shear) or 0.3 Pa (high shear). In chambers coated with P-selectin, adherent leukocytes rolled. By use of a P-selectin-Fc fragment chimera, adhesion was predominantly stationary, enabling definition of initial attachment sites. Neutrophils adhered in all regions of the low-shear chamber, with a local maximum around the reattachment point. However, in the high-shear chamber, adhesion was restricted to the recirculation zone and immediately downstream from the reattachment point. Rolling at high shear stress allowed a population of regions where initial attachment could not occur. At high shear, lymphocytes and monocytes also formed attachments restricted to the region of the reattachment point. The results imply that all types of leukocytes might bind to a capture receptor in high-shear vessels with discontinuities in the wall and might then spread to other regions.