Binding of [125I]Shiga-like Toxin-1 to Human Endothelial Cells: Implications for the Pathogenesis of Shiga Toxin-associated Hemolytic Uremic Syndrome

Abstract

Renal glomerular endothelial cell damage is a hallmark of Shiga toxin-associated hemolytic uremic syndrome (HUS) following bacillary dysentery in humans. This study examined the binding of [125I]Shiga-like toxin-1 (SLT-I) to human umbilical vein endothelial cells (HUVEC) and to human renal glomerular microvascular endothelial cells (HRMEC) in vitro, in relation to the sensitivity of these endothelial cells to Shiga toxin. HUVEC isolated from individual umbilical cords differed in their sensitivity to Shiga toxin. These HUVEC isolates also differed in their expression of the receptor for SLT-1 (3.6 x lo5 and 2.0 x 105 receptors/cell for sensitive and moderately sensitive HUVEC, respectively). Bacterial lipopolysaccharide (LPS) sensitized HUVEC to Shiga toxin and induced a corresponding 2.5-fold increase in SLT-1 receptor expression on HUVEC. HRMEC are the putative target of Shiga toxins during HUS and were much more sensitive to Shiga toxin than were HUVEC (LD,, = 0.1 pM vs. 10 nM, respectively). HRMEC also expressed at least 200- to 360-fold more SLT-1 receptors (27.2 x 107 receptors/cell) than did HUVEC. These results suggest that Shiga toxin receptor expression in different endothelial cells may determine the degree of sensitivity of different endothelial cells to Shiga toxin and may be important in determining the susceptibility of different vascular beds to Shiga toxin-mediated disease.