ENDOTHELIAL HETEROGENEITY IN SHIGA TOXIN RECEPTORS AND RESPONSES

This study addresses the basis for regional microvascular susceptibili ty to bacterial toxins implicated in hemolytic uremic syndrome. The re sults indicate a relationship between the degree of Shiga toxin sensit ivity of human endothelial cells from different sources and the amount of globotriaosylceramide (Gb3) glycosphingolipid receptor for Shiga t oxin expressed by these cells. Cell viability and protein synthesis of renal endothelial cells were reduced to 50% by 1 pM Shiga toxin, whil e umbilical vein cells were not affected by >1 nM toxin. Similarly, ba sal levels of Gb3 were approximately 50 times higher in renal endothel ial cells than in the umbilical endothelial cells. Pre-exposure of umb ilical endothelial cells to tumor necrosis factor-alpha or bacterial l ipopolysaccharide increased Gb3 content 4-6-fold coincident with incre ases in sensitivity to cytotoxic and protein synthesis inhibitory effe cts of Shiga toxin. Lipopolysaccharide induction of both Gb3 and sensi tivity to Shiga toxin cytotoxic action in umbilical endothelial cells was dependent on the structure of lipopolysaccharide. Neither tumor ne crosis factor-alpha nor lipopolysaccharide altered the Shiga toxin sen sitivity or the Gb3 content of renal endothelial cells. These data ind icate that differential endothelial expression of glycolipid receptors for Shiga toxins may be responsible for localized involvement of the kidney in hemolytic uremic syndrome.