Effects of disturbed flow on leukocyte-endothelial cell adhesion

Leukocytes preferentially adhere to vascular endothelial cells at vascular branches and curvatures. This suggests that complex flow structures can exert significant influences on leukocyte-endothelial cell adhesion. The effects of local disturbed flow on leukocyte adhesion to cultured human umbilical vein endotheiial cells (ECs) were studied m vitro by using a well defined verticalstep flow (VSF) channel. Leukocyte adhesion to ECs pre-exposed to VSF for 24 h was significantly enhanced, as compared with static samples, but no significant differences in adhesion were seen at different flow structure areas. In addition, the EC surface expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin were significantly increased by exposing ECs to VSF for 24 h, but not vascular adhesion molecule-1 (VCAM-1). However, the flow-induced expressions of ICAM-1 and E-selectin showed no differences among different flow areas. Anti-ICAM-1 antibody significantly blocked leukocyte adhesion to ECs under disturbed flow. When ECs were treated with tumor necrosis factor-a (TNF-a), the leukocyte adhesion was dramatically increased in the disturbed flow areas, especially in flow stagnation and reattachment areas. The results demonstrate that the effects of disturbed flow can selectively modulate the EC surface expression of adhesive molecules and enhance leukocyte adhesion to ECs. and that complex local hemodynamic flow structures can have profound impact on the adhesion of leukocytes to ECs when the ECs are activated. (Supported by Academia Sinica.' ROC-NSC BI -00-0047, and NIH grants HL 43026 and HL 44147).