SHEAR-STRESS INHIBITS ADHESION OF CULTURED MOUSE ENDOTHELIAL-CELLS TO LYMPHOCYTES BY DOWN-REGULATING VCAM-1 EXPRESSION

Monolayers of endothelial cells (EC) cultured from mouse lymph nodes were exposed to controlled levels of shear stress (0-7.1 dyn/cm(2)) in a parallel plate flow chamber, and binding between the flow-loaded EC and mouse lymph node-derived lymphocytes was assayed. A large number of lymphocytes adhered to the stationary control EC, but in EC exposed to a shear stress of 1.5 dyn/cm(2) for 6 h, the adhesion decreased to 68.8 +/- 12.8% (SD; n = 19) of control (n = 29, P < 0.001). The decrease in adhesion induced by flow loading was time and shear stress dependent and reversible. Treatment of stationary EC with a monoclonal antibody (MAb) to vascular cell adhesion molecule-1 (VCAM-1) reduced the adhesion to 70.6 +/- 11.5% (n = 19) of control (P < 0.001), whereas MAb to CD44 and to intercellular adhesion molecule-1 had no effect on it. Flow cytometric analysis revealed that the amount of VCAM-1 expressed on the cell surface was decreased to 48.5 +/- 15.8% (n = 6) of control by flow loading (P < 0.001). Flow loading experiments using two perfusates with different viscosities demonstrated that the decrease in VCAM-1 expression due to flow was shear stress rather than shear rate dependent. The detection of mRNA by reverse transcriptase-polymerase chain reaction showed that VCAM-1 mRNA levels were markedly depressed in EC exposed to flow loading. These results, demonstrating that flow loading suppressed the adhesiveness of mouse lymph node EC to lymphocytes by downregulating the expression of VCAM-1 by EC, suggest that fluid shear stress can affect the adhesive interaction between EC and lymphocytes by modulating adhesion molecule expression at both mRNA and surface protein levels.