Abstract
Hemolytic uremic syndrome (HUS) is characterized by a triad of symptoms consisting of hemolytic anemia, thrombocytopenia and acute renal failure. The most common form of HUS is caused by an infection with Shiga toxin (Stx) producing Escherichia coli bacteria (STEC-HUS), and the kidneys are the major organs affected. The development of HUS after an infection with Stx occurs most frequently in children under the age of 5 years. However, the cause for the higher incidence of STEC-HUS in children compared to adults is still not well understood. Human glomerular microvascular endothelial cells (HGMVECs) isolated and cultured from pediatric and adult kidney tissue were investigated with respect to Stx binding and different cellular responses. Shiga toxin-1 (Stx-1) inhibited protein synthesis in both pediatric and adult HGMVECs in a dose-dependent manner at basal conditions. The preincubation of pediatric and adult HGMVECs for 24 hrs with TNFα resulted in increased Stx binding to the cell surface and a 20–40% increase in protein synthesis inhibition in both age groups. A decreased proliferation of cells was found when a bromodeoxyuridine (BrdU) assay was performed. A trend towards a delay in endothelial wound closure was visible when pediatric and adult HGMVECs were incubated with Stx-1. Although minor differences between pediatric HGMVECs and adult HGMVECs were found in the assays applied in this study, no significant differences were observed. In conclusion, we have demonstrated that in vitro primary HGMVECs isolated from pediatric and adult kidneys do not significantly differ in their cell biological responses to Stx-1.
Highlights
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy with hemolytic anemia, thrombocytopenia and the kidneys are the major organs affected
The proliferation of Human glomerular microvascular endothelial cells (HGMVECs) was investigated after the preincubation of cells with 10 ng/mL of TNFα and incubation of cells with 0.1 to 1000 pM Shiga toxin (Stx)-1 for 24 h
The effect of Shiga toxin type 1 (Stx-1) on the migration of HGMVECs was investigated by using an endothelial wound closure assay
Summary
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy with hemolytic anemia, thrombocytopenia and the kidneys are the major organs affected. Infection with Shiga toxin (Stx) producing Escherichia coli bacteria (STEC) is one of the causes for the development of HUS (STEC-HUS) and is mostly seen in children under the age of 5 years [1]. The reason for a higher incidence of STEC-HUS in children compared to adults is still not understood. There was no significant difference between the pediatric vs adult control groups or the pediatric vs adult TNFα groups, in their ability to bind Alexa 488-labeled Stx-B (p = 0.145 for ctrl and p = 0.066 for TNFα by Mann−Whitney test). Experiments were performed three times for pediatric donor I and II, adult donor I and III. Experiments were performed twice for adult donor II and once for adult donor IV
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
