Tumor necrosis factor alpha increases human cerebral endothelial cell Gb(3) and sensitivity to Shiga toxin

Hemolytic uremic syndrome (HUS) is associated with intestinal infection by enterohemorrhagic Escherichia coli strains that produce Shiga toxins. Globo triaosylceramide (Gb(3)) is the functional receptor for Shiga toxin, and tu mor necrosis factor alpha (TNF-alpha) upregulates Gb(3) in both human macro vascular umbilical vein endothelial cells and human microvascular brain end othelial cells. TNF-alpha treatment enhanced Shiga toxin binding and sensit ivity to toxin. This upregulation was specific for Gb(3) species containing normal fatty acids (NFA). Central nervous system (CNS) pathology in HUS co uld involve cytokine-stimulated elevation of endothelial NFA-Gb(3) levels. Differential expression of Gb(3) species may be a critical determinant of S higa toxin toxicity and of CNS involvement in HUS.