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Infect Immun, February 1998, p. 636-644, Vol. 66, No. 2
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Apoptosis of Renal Cortical Cells in the Hemolytic-Uremic Syndrome: In Vivo and In Vitro Studies

Diana Karpman,1,2,* Anders Håkansson,1 Maria-Thereza R. Perez,3 Christina Isaksson,2 Eric Carlemalm,4 Alfredo Caprioli,5 and Catharina Svanborg1

Departments of Medical Microbiology,1 Pediatrics,2 Ophthalmology,3 and Electron Microscopy,4 University of Lund, S-22185 Lund, Sweden, and Istituto Superiore di Sanità, Laboratorio di Medicina Veterinaria, 00161 Rome, Italy5

Received 6 August 1997/Returned for modification 18 September 1997/Accepted 17 November 1997

This study examined apoptotic cell death associated with Shiga-like toxin (Stx)-producing Escherichia coli. Renal cortices from three children with postenteropathic hemolytic-uremic syndrome (HUS) and from mice infected with E. coli O157:H7 and pediatric renal tubular epithelial cells stimulated with Stx and E. coli O157:H7 extracts were examined for apoptotic changes. Apoptotic cells were detected by terminal dUTP nick end labeling of tubuli and glomeruli from HUS patients and from mice inoculated with Stx-2-positive and Stx-negative strains. Apoptosis was more extensive and severe ultramorphological nuclear and cytoplasmic changes were seen in the Stx-2-positive group. Stx caused DNA fragmentation and ultramorphological changes indicating apoptosis in cultured pediatric tubular cells. DNA fragmentation increased when cells were prestimulated with tumor necrosis factor alpha. Polymyxin extracts from Stx-2-positive and Stx-negative strains induced DNA fragmentation, but only extracts from Stx-2-positive strains caused ultramorphological changes and extensive DNA fragmentation. The results indicate that HUS is accompanied by increased apoptosis of kidney cells and that bacterial factors, possibly together with host cytokines in vivo, may activate apoptotic tissue injury.

* Corresponding author. Mailing address: Department of Pediatrics, University of Lund, 22185 Lund, Sweden. Phone: 46-46-171000. Fax: 46-46-145459. E-mail: diana.karpman{at}mmb.lu.se.




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