Alpha(1,3)-fucosyltransferase VII-dependent synthesis of P- and E-selectin ligands on cultured T lymphoblasts

T lymphocytes up-regulate the synthesis of ligands for E- and P-selectin during proliferative responses in vivo and in vitro. Previous studies from our laboratories indicated that the alpha(1,3)-fucosyltransferase FucT-VII regulates the synthesis of E-Selectin ligands and sialylated Lewis(x)-related epitopes (sLe(x)-related epitopes) in human T lymphoblasts. The current report shows that production of both P- and E-Selectin ligands is FucT-VII dependent, but peak synthesis of each occurs at different levels of fucosyltransferase activity in intact cells. In brief, FucT-VII mRNA levels were higher in cultured T lymphoblasts expressing sLe(x)-related epitopes and both Selectin ligands than in cells expressing P-selectin ligands alone. However, synthesis of the epitopes and both Selectin ligands required the FucT-VII Enzyme in transfected Molt-4 cells. In contrast, neither constitutive nor transfection-enhanced levels of the FucT-IV Enzyme generated active P-selectin ligands in these lines. In addition, targeted deletion of the FucT-VII gene in mice markedly inhibited the synthesis of both P- and E-Selectin ligands during blast transformation in vitro. Finally, the optimal synthesis of active P-selectin ligands occurred at lower level of FucT-VII activity than required for synthesis of equally active E-Selectin ligands in both cultured T lymphoblasts and FucT-VII transfectants. Consequently, the FucT-VII Enzyme is essential for the synthesis of both P- and E-Selectin ligands by T lymphoblasts, and its activity determines whether P-selectin ligands are expressed alone or in conjunction with E-Selectin ligands and sLe(x)-related epitopes on human T cells.