Expression of ICAM-1 and VCAM-1 and Monocyte Adherence in Arteries Exposed to Altered Shear Stress

Abstract Local shear stresses generated by blood flow exert direct mechanical effects on adhesion of circulating leukocytes to vascular endothelium, but their effects on expression of endothelial-leukocyte adhesion molecules have not been determined. Shear stress in rabbit carotid arteries was increased by 170% or decreased by 73% in 5 days by surgical manipulations. En face immunofluorescence staining with the monoclonal antibody Rb1/9 revealed that vascular cell adhesion molecule–1 (VCAM-1) expression was greatly increased under low shear stress, but the distribution 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. Occasionally, small islands of cells were labeled intensely. Monocytes, detected by use of the monocyte-specific antibody HAM 56, adhered to endothelium 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 regions were devoid of monocytes. VCAM-1 expression also increased significantly but to a lesser extent when shear stress was approximately doubled. Thus, 8.7±1.5% of fields were VCAM-1 positive under high shear versus 2.5±0.87% under normal shear stress. No monocytes were detected at high shear stress. At normal shear stresses, intercellular adhesion molecule–1 (ICAM-1), detected by use of the monoclonal antibody Rb2/3, was extensively distributed; thus, 53.5±5.5% of fields contained ICAM-1–positive cells. The junctional regions of the cells were heavily stained. Experimental increases in shear stress significantly upregulated ICAM-1 expression (88.3±2.0% of fields were ICAM-1 positive; P<.05). Staining was again concentrated in the cell junctional regions. Reduced shear stress suppressed ICAM-1 expression (16.6±10.3% of fields were positive), and ICAM-1 was more commonly, but not exclusively, distributed diffusely. Junctional ICAM-1 may participate in endothelial cell-cell adhesion; alternatively, a pool of ICAM-1 concentrated between cell junctions may be inaccessible to circulating leukocytes until endothelial cell activation presents the molecule to the vessel lumen.