Comparison of the effects of shiga-like toxin 1 on cytokine- and butyrate-treated human umbilical and saphenous vein endothelial cells

To examine the reported heterogeneity of endothelial cells to Shiga-like toxin 1 (Stx1), the responses of human umbilical (HUVEC) and saphenous (HSVEC) vein endothelial cells to cytokines, butyrate, and toxin were compared. Untreated HSVEC were generally more susceptible than were HUVEC to Stxl; pretreatment of either cell with lipopolysaccharide, interleukin-1 beta, or tumor necrosis factor-alpha enhanced Stxl toxicity, Dexamethasone alone increased total globotriaosylceramide (Gb3) content and toxin binding but inhibited cytokine-enhanced cytotoxicity, whereas the differentiation agent, sodium butyrate, increased both Gb3 content and cytotoxicity responses to Stxl, most prominently in HSVEC. Stxl toxicity directly correlated with the release of von Willebrand factor from HSVEC but not from HUVEC. Thus, HUVEC and HSVEC exhibit distinctive responses to Stxl, cytokines, and butyrate. This suggests the need for caution in extrapolating from in vitro studies utilizing one endothelial cell type to in vivo events during pathogenesis of Stx-mediated thrombotic microangiopathies.