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

Monolayers of endothelial cells (EC) cultured from mouse lymph nodes w ere 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 o f 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 decrea se in adhesion induced by flow loading was time and shear stress depen dent and reversible. Treatment of stationary EC with a monoclonal anti body (MAb) to vascular cell adhesion molecule-1 (VCAM-1) reduced the a dhesion 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 contro l by flow loading (P < 0.001). Flow loading experiments using two perf usates with different viscosities demonstrated that the decrease in VC AM-1 expression due to flow was shear stress rather than shear rate de pendent. The detection of mRNA by reverse transcriptase-polymerase cha in reaction showed that VCAM-1 mRNA levels were markedly depressed in EC exposed to flow loading. These results, demonstrating that flow loa ding 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 lympho cytes by modulating adhesion molecule expression at both mRNA and surf ace protein levels.