CELL-SURFACE P-SELECTIN AND E-SELECTIN SUPPORT SHEAR-DEPENDENT ROLLING OF BOVINE GAMMA DELTA-T-CELLS/

The vascular selectins P- and E-selectin are inducible adhesion protei ns expressed by endothelial cells that have been shown to support shea r-dependent rolling of myeloid cells. This interaction is thought to b e a prerequisite event for subsequent steps, such as tight adhesion/ag gregation and transendothelial cell migration, involved in the accumul ation of leukocytes into tissues. Certain lymphocyte subsets have also been shown to bind the vascular selectins, but the importance of this interaction in mediating shear-dependent rolling, as described for my eloid cells, has not been demonstrated. We expand on our earlier obser vation that bovine gamma/delta T cells bind E-selectin by showing that this interaction leads to a reproducible rolling event in assays done under shear forces that approximate those that occur in vivo. E-selec tin, expressed by L cell transfectants or cytokine-stimulated human an d bovine endothelial cells, equally supports the shear-dependent rolli ng interaction. The lymphocyte adhesion proteins L-selectin, CD44, and CD2 do not contribute to this event. Neuraminidase treatment of the g amma/delta T cells or addition of EDTA to the assay completely blocks the rolling interaction. We further show for the first time that P-sel ectin expressed by thrombin-activated platelets or a soluble P-selecti n/human Ig chimera specifically binds gamma/delta T cells. The P-selec tin interaction is similar to the rolling event mediated by E-selectin -it requires divalent cations and sialic acid on the lymphocyte, it la cks involvement of L-selectin and CD44, and rolling occurs under physi ologic shear conditions. These results provide the documentation that the vascular selectins can support shear-dependent rolling of a lympho cyte subset and that P-selectin mediates the adhesion of gamma/delta T cells.