EXPRESSION OF ICAM-1 AND VCAM-1 AND MONOCYTE ADHERENCE IN ARTERIES EXPOSED TO ALTERED SHEAR-STRESS

Local shear stresses generated by blood flow exert direct mechanical e ffects on adhesion of circulating leukocytes to vascular endothelium, but their effects on expression of endothelial-leukocyte adhesion mole cules have not been determined. Shear stress in rabbit carotid arterie s was increased by 170% or decreased by 73% in 5 days by surgical mani pulations. En face immunofluorescence staining with the monoclonal ant ibody Rb1/9 revealed that vascular cell adhesion molecule-1 (VCAM-1) e xpression was greatly increased under low shear stress, but the distri bution of staining was patchy. Thus, 71.4+/-7.8% of fields were VCAM-1 positive versus 2.4+/-0.47% of fields in control arteries. Frequently , large regions showed consistent but heterogeneous staining. Occasion ally, small islands of cells were labeled intensely. Monocytes, detect ed by use of the monocyte-specific antibody HAM 56, adhered to endothe lium under low shear stress; 64.5+/-8.2% of the monocytes colocalized with detectable VCAM-1, although many (83.2+/-2.8%) VCAM-1-positive re gions were devoid of monocytes. VCAM-1 expression also increased signi ficantly but to a lesser extent when shear stress was approximately do ubled. Thus, 8.7+/-1.5% of fields were VCAM-1 positive under high shea r versus 2.5+/-0.87% under normal shear stress. No monocytes were dete cted at high shear stress. At normal shear stresses, intercellular adh esion molecule-1 (ICAM-1), detected by use of the monoclonal antibody Rb2/3, was extensively distributed; thus, 53.5+/-5.5% of fields contai ned ICAM-1-positive cells. The junctional regions of the cells were he avily stained. Experimental increases in shear stress significantly up regulated ICAM-1 expression (88.3+/-2.0% of fields were ICAM-1 positiv e; P<.05). Staining was again concentrated in the cell junctional regi ons. Reduced shear stress suppressed ICAM-1 expression (16.6+/-10.3% o f fields were positive), and ICAM-1 was more commonly, but not exclusi vely, distributed diffusely. Junctional ICAM-1 may participate in endo thelial cell-cell adhesion; alternatively, a pool of ICAM-1 concentrat ed between cell junctions may be inaccessible to circulating leukocyte s until endothelial cell activation presents the molecule to the vesse l lumen.