Fluid shear stress modulates surface expression of adhesion molecules by endothelial cells

Blood. 1995 Apr 1;85(7):1696-703.

Abstract

We investigated the effect of hemodynamic shear forces on the expression of adhesive molecules, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVEC) exposed to laminar (8 dynes/cm2) or turbulent shear stress (8.6 dynes/cm2 average), or to a static condition. Laminar flow induced a significant time-dependent increase in the surface expression of ICAM-1, as documented by flow cytometry studies. Endothelial cell surface expression 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 modulated by the flow condition. Turbulent flow did not affect surface expression of either E-selectin or ICAM-1. To evaluate the functional significance of the laminar-flow-induced increase in ICAM-1 expression, we studied the dynamic interaction of total leukocyte suspension with HUVEC exposed to laminar flow (8 dynes/cm2 for 6 hours) in a parallel-plate flow chamber or to static condition. Leukocyte adhesion to HUVEC pre-exposed to flow was significantly enhanced, compared with HUVEC maintained in static condition (233 +/- 67 v 43 +/- 16 leukocytes/mm2, respectively), and comparable with that of interleukin-1 beta treated HUVEC. Mouse monoclonal antibody anti-ICAM-1 completely blocked flow-induced upregulation of leukocyte adhesion. Interleukin-1 beta, which upregulated E-selectin expression, caused leukocyte rolling on HUVEC that 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 endothelial cells and promotes leukocyte adhesion. These data are relevant to the current understanding of basic mechanisms that govern local inflammatory reactions and tissue injury.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Adhesion Molecules / genetics
  • Cells, Cultured
  • E-Selectin
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation*
  • Humans
  • Infant, Newborn
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-1 / pharmacology
  • Leukocytes / cytology
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Rheology
  • Stress, Mechanical*
  • Umbilical Veins

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • E-Selectin
  • Interleukin-1
  • Membrane Proteins
  • Intercellular Adhesion Molecule-1