APOPTOSIS OF RENAL CORTICAL-CELLS IN THE HEMOLYTIC-UREMIC SYNDROME - IN-VIVO AND IN-VITRO STUDIES

This study examined apoptotic cell death associated with Shiga-like to xin (Stx)-producing Escherichia coli, Renal cortices from three childr en 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 f or apoptotic changes, Apoptotic cells were detected by terminal dUTP n ick end labeling of tubuli and glomeruli from HUS patients and from mi ce inoculated with Stx-2-positive and Stx-negative strains, Apoptosis was more extensive and severe ultramorphological nuclear and cytoplasm ic changes were seen in the Stx-2-positive group. Stx caused DNA fragm entation and ultramorphological changes indicating apoptosis in cultur ed pediatric tubular cells, DNA fragmentation increased when cells wer e prestimulated with tumor necrosis factor alpha, Polymyxin extracts f rom Stx-2-positive and Stx-negative strains induced DNA fragmentation, but only extracts from Stx-2-positive strains caused ultramorphologic al changes and extensive DNA fragmentation, The results indicate that HUS is accompanied by increased apoptosis of kidney cells and that bac terial factors, possibly together with host cytokines in vivo, may act ivate apoptotic tissue injury.