The shear threshold effect for adhesion through L-selectin: influence of receptor and ligand site density

The selectin family of cell adhesion molecules mediates capture and rolling adhesion of white blood cells to vascular walls, an essential component of the inflammatory response. Adhesion through L-selectin requires a hydrodynamic shear stress above a threshold level, a phenomenon known as the shear threshold effect. We have reported that the shear threshold effect can be re-created in cell-free systems, in which ligand-coated microspheres are perfused over L-selectin-coated surfaces. The paper extends the use of the cell-free system to determine the concurrent influence of L-selectin and ligand site density on the shear threshold effect. We find that the shear threshold effect diminishes with increasing levels of both L-selectin and its ligand. At reduced site densities of either L-selectin or ligand, the shear threshold effect is present, with maximal rolling observed at a shear stress of 1.2 dynes/cm². At higher site densities of L-selectin and ligand, the shear threshold effect disappears. These results suggest that a shear threshold is required for L-selectin-mediated rolling only when low numbers of receptor-ligand bonds can be formed. The appearance of the shear threshold effect may be controlled via receptor or ligand site density.