ESPN 53rd Annual Meeting

ESPN 2021


 
Comparison of cell biological responses after Shiga toxin-1 exposure to primary human glomerular microvascular endothelial cells from pediatric and adult origin
WOUTER J.C. FEITZ 1 PETRA A. VAN SETTEN 1 THEA J.A.M. VAN DER VELDEN 1 CHRISTOPH LICHT 2 LAMBERT P.J.W. VAN DEN HEUVEL 1 NICOLE C.A.J. VAN DE KAR 1

1- AMALIA CHILDRENS HOSPITAL, RADBOUDUMC, NIJMEGEN, THE NETHERLANDS
2- THE HOSPITAL FOR SICK CHILDREN, TORONTO, ON, CANADA
 
Introduction:

The 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. 

Material and methods:

In this study, primary 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. 

Results:

Shiga toxin type 1 (Stx-1) inhibited protein synthesis in both pediatric and adult HGMVECs in a dose-dependent manner. Preincubation with TNFα resulted in increased Stx binding and a 20-40% increase in protein synthesis inhibition in both age groups. 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 HGMVECs were incubated with Stx-1. Although minor variations between pediatric HGMVECs and adult HGMVECs were found in this study, it was not significant.

Conclusions:

In conclusion, in vitro primary HGMVECs isolated from pediatric and adult kidneys do not differ in their cell biological responses to Stx-1. With this in mind, we hypothesize that other extrinsic or genetic factors contribute to the sensitivity of the glomerular endothelium and the pathophysiology of STEC-HUS in young children.