FLUID SHEAR-STRESS MODULATES SURFACE EXPRESSION OF ADHESION MOLECULESBY ENDOTHELIAL-CELLS

We investigated the effect of hemodynamic shear forces on the expressi on of adhesive molecules, E-selectin, and intercellular adhesion molec ule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVEC) expos ed to laminar (8 dynes/ cm(2)) or turbulent shear stress (8.6 dynes/cm (2) average), or to a static condition. Laminar flow induced a signifi cant time-dependent increase in the surface expression of ICAM-1, as d ocumented by flow cytometry studies. Endothelial cell surface expressi on of ICAM-1 in supernatants of HUVEC exposed to laminar flow was not modified, excluding the possibility that HUVEC exposed to laminar flow synthetize factors that upregulate ICAM-1. The effect of laminar flow was specific for ICAM-1, while E-selectin expression was not modulate d by the flow condition. Turbulent flow did not affect surface express ion of either E-selectin or ICAM-1. To evaluate the functional signifi cance of the laminar-flow-induced increase in ICAM-1 expression, we st udied the dynamic interaction of total leukocyte suspension with HUVEC exposed to laminar flow (8 dynes/cm(2) for 6 hours) in a parallel-pla te flow chamber or to static condition. Leukocyte adhesion to HUVEC pr e-exposed to flow was significantly enhanced, compared with HUVEC main tained in static condition (233 +/- 67 v 43 +/- 16 leukocytes/mm(2), r espectively), and comparable with that of interleukin-1 beta treated H UVEC. Mouse monoclonal antibody anti-ICAM-1 completely blocked flow-in duced upregulation of leukocyte adhesion. Interleukin-1 beta, which up regulated E-selectin expression, caused leukocyte rolling on HUVEC tha t was significantly lower on flow-conditioned HUVEC and almost absent on untreated static endothelial cells. Thus. laminar flow directly and selectively upregulates ICAM-1 expression on the surface of endotheli al cells and promotes leukocyte adhesion. These data are relevant to t he current understanding of basic mechanisms that govern local inflamm atory reactions and tissue injury. (C) 1995 by The American Society of Hematology.