Leukocyte Adhesion Deficiency Type II (LAD II) is a recently described syndrome and the two patients with this defect lack fucosylated
glycoconjugates. These
glycoconjugates include the
selectin ligand, sialyl LewisX, and various fucosylated
blood group antigens. To date, the molecular anomaly in these patients has not been identified. We localized the defect in LAD II to the de novo pathway of
GDP-fucose biosynthesis, by inducing cell-surface expression of fucosylated
glycoconjugates after exposure of lymphoblastoid cell lines from the LAD II patients to exogenous
fucose. This defect is not restricted to hematopoietic cells, since similar findings were elicited in both human umbilical vein endothelial cells (HUVEC) and fibroblasts derived from an affected abortus. We have used these LAD II endothelial cells to examine the consequence of fucosylation of endothelial cells on the rolling of normal neutrophils in an in vitro assay. Neutrophil rolling on LPS-treated normal and LAD II HUVEC was inhibited by an
E-selectin monoclonal antibody at both high and low shear rates. LAD II HUVEC lacking fucosylated
glycoproteins supported leukocyte rolling to a similar degree as normal HUVEC or LAD II cells that were
fucose-fed. At low shear rates, an
L-selectin antibody inhibited neutrophil rolling to a similar degree whether the LAD II cells had been
fucose-fed or not. These findings suggest that fucosylation of nonlymphoid endothelial cells does not play a major role in neutrophil rolling and that
fucose is not a critical moiety on the
L-selectin ligand(s) on endothelial cells of the systemic vasculature.