Down-Regulation of Vascular Adhesion Molecule-1 by Fluid Shear Stress in Cultured Mouse Endothelial Cellsa

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Abstract
This study was undertaken to determine whether blood flow modulates the adhesive property of vascular endothelial cells to lymphocytes and, if it does, what adhesion molecules are involved. Cultured mouse endothelial cells were exposed to medium flow in a parallel plate chamber, and binding assay using fluorescence-labeled lymphocytes was carried out. The adhesion rate of endothelial cells to lymphocytes, which was high in the static control state, decreased when exposed to shear stress (1.5 dynes/cm2) for 6 h. The treatment of static endothelial cells with a monoclonal antibody of vascular cell adhesion molecule-1 (VCAM-1) depressed the adhesion rate to the same extent as that caused by flow, while monoclonal antibodies of CD44 and intercellular adhesion molecule-1 had no effect on it. Flow cytometric analysis revealed that the application of flow decreased markedly the amount of VCAM-1 expressed on the cell surface. A reverse transcriptase-polymerase chain reaction of mRNA showed that flow depressed VCAM-1 mRNA levels. These results suggest that blood flow can modulate the adhesive property of endothelial cells to lymphocytes via affecting the surface expression of adhesion molecules, e.g., down-regulation of VCAM-1.

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