Most childhood (diarrheal) hemolytic uremic syndrome (HUS) is associated with VT produced by E.coli or Shigella. VT-1 is a member of the holotoxin family of Shiga-like toxins (SLT) which inhibit protein synthesis in susceptible cells and thereby lead to cell injury and death. We previously demonstrated that VT-1 is a direct cytotoxin for human glomerular cells. In renal biopsy specimens from children with HUS, tubular cell toxicity and necrosis are often observed. In this study we sought to determine whether VT-1 is directly cytotoxic for human PTEC.

PTEC isolated from normal human kidney were exposed to VT-1 (0.1 pM to 1 nM) for 6 to 48 hr. Cytotoxicity was determined by calcein-AM uptake of viable cells. PTEC were susceptible to VT-1 in a dose and time dependent manner with maximum cytotoxicity after 48 hr exposure to VT-1. PTEC morphology was altered after 6 hr exposure to VT-1 with irregular cell shape and cell detachment more prominent with longer exposure. Radiolabeled VT-1 binding studies demonstrated that PTEC expressed a receptor for VT-1. PTEC were less sensitive to VT-1 than human GCEC (VT-1 10 pM = 58% cell survival @ 24 hr, 35% @ 48 hr).Table

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Although less sensitive than GCEC to equivalent doses of VT-1, the susceptibility of PTEC to VT-1 may influence the renal manifestations of HUS in affected children.