Apoptosis of Renal Tubular Cells in Shiga-Toxin-Mediated Hemolytic Uremic Syndrome

Abstract

In order to clarify the mechanism of unusual renal tubular dysfunction seen in a child with Shiga toxin (Stx)-mediated hemolytic uremic syndrome (HUS), we studied the renal biopsy specimens for Stx binding and apoptosis of renal tubular cells. A 7-year-old boy with Stx-2-mediated HUS demonstrated extensive renal tubular damage characterized by nonoliguric acute renal failure, increased urinary tubular enzymes and defective urine-concentrating capacity. His renal biopsy specimens were analyzed for Stx binding and apoptotic cell death. Seven kidney tissue specimens obtained from patients without HUS served as controls. Detection of Stx binding to renal sections and apoptotic cells were performed using mouse monoclonal anti-Stx 2 antibody and the TUNEL method, respectively. Positive staining was observed predominantly in renal tubular cells, while the 7 kidney tissue specimens from control patients did not show positive staining. To the best of our knowledge, this is the first case to show Stx binding and apoptotic cell death in renal tubules on biopsy specimens obtained from a child with Stx-mediated HUS. In conclusion, this case suggests that vascular endothelial cells are not the sole nor the consistent target for Stx-mediated cell injury and that significant renal tubular damage other than glomerular damage might occur in some children with Stx-mediated HUS.

Shiga toxin binding to globotriaosyl ceramide induces intracellular signals that mediate cytoskeleton remodeling in human renal carcinoma-derived cells

“…In vitro experiments have revealed that Stx1 induces cell death in renal tubular epithelial cells through protein synthesis inhibition and apoptosis (Karpman et al, 1998;Kiyokawa et al, 1998;Taguchi et al, 1998;Williams et al, 1999). Several clinical studies have indicated the involvement of renal tubular damage during the course of HUS (Kaneko et al, 2001;Takeda et al, 1993). The appearance of apoptotic cells in the renal tubules of the kidney in HUS patients, accompanied by STEC infection, further indicates that renal tubular injury does occur in the kidneys of HUS patients (Karpman et al, 1998;Taguchi et al, 1998).…”

Studies on PCR-Based Rapid Detection Systems for Salmonella spp.

“…In this study, genes encoding the virulence determinants and their expression regulator have been used to characterize numerous bacteria. A molecular test based on the detection of shiga-like toxin (verotoxin type II), femA (cytoplasmic protein), toxR (trans-membrane DNA binding protein), iap (invasive associative protein), and invA (invasion protein A) genes has been applied for identification of E. coli O157:H7 (Jinneman et al, 2003;Kaneko et al, 2001;Karpman et al, 1998;Schmidt et al, 1995;Wang et al, 2002), Staphylococcus aureus (Mehrotra et al, 2000), Vibrio parahaemolyticus (Karpman et al, 1998;Cabrera-Garcia et al, 2004), Listeria monocytogenes (Bubert et al, 1992;Bubert et al, 1999;Volokhov et al, 2002), and Salmonella spp. (Chiu et al, 1996).…”

Curcumin Decreases Binding of Shiga-Like Toxin-1B on Human Intestinal Epithelial Cell Line HT29 Stimulated with TNF-.ALPHA. and IL-1.BETA.: Suppression of p38, JNK and NF-.KAPPA.B p65 as Potential Targets

“…Because the IECs are the first line in contact with Stx in a host, the interaction of Stx with epithelium may be a pivotal role in HUS 3) through induction of apoptosis in vivo and in vitro studies. [7][8][9][10] Apoptosis of IECs could destroy the barriers in host lumen and permit Stx to enter the bloodstream and attack the central nervous and/or renal systems. 5,11) In many cells, Stx-induced apoptosis has been induced by cleavage of poly(ADP-ribose) polymerase, release of cytochrome C and capase-3 activities with mitogen-activated protein kinases (MAPKs).…”