Induction of apoptosis of human brain microvascular endothelial cells by shiga toxin 1.

Brain injury is the most frequent cause of mortality among patients with the hemolytic-uremic syndrome. Human brain endothelial cells (HBECs) are resistant to Escherichia coli-derived Shiga toxin (Stx); however, inflammatory cytokines markedly increase HBEC sensitivity to Stx cytotoxicity. HBECs were exposed to tumor necrosis factor (TNF)-alpha, with and without Stx-1, and cell survival, (125)I-Stx1 binding, globotriaosylceramide content, cell necrosis, and cell apoptosis levels were determined. TNF greatly increased Stx-1 cytotoxicity, primarily through induction of apoptosis, in HBEC.