title: Shigatoxin-1 binding and receptor expression in human kidneys do not change with age.
abstract: Postdiarrheal hemolytic-uremic syndrome (D+HUS) occurs predominantly in young children. The rarity of D+HUS in adults has been ascribed to aging-associated loss of glomerular globotriaosylceramide (Gb3) expression, the major cognate receptor for shigatoxin. This belief, however, is based on relatively little data. The current study was undertaken to examine renal shigatoxin-1 (Stx-1) binding and Gb3 expression by human kidneys from varying aged subjects. Immunofluorescent staining and thin layer chromatography of neutral lipid extracts were performed. Abundant Stx-1 binding to both glomeruli and tubules was observed in frozen renal sections from all subjects of all ages (6 months to 85 years). The pattern of Stx-1 binding was identical between adults and children, with glomerular endothelial cells and cortical tubules being strongly labeled. Stx-1 binding affinity was similar between pediatric and adult kidneys. Antibodies to Gb3 showed a similar pattern and degree of staining regardless of donor age. In addition, Gb3 levels in glomeruli and tubules isolated from fresh kidney tissue were comparable between different aged donors. These data demonstrate that intrinsic renal binding of Stx-1 does not vary with age. It is suggested that factors other than basal renal Gb3 expression account for the age-related incidence of acute renal failure in D+HUS.
authors.affiliation: Division of Nephrology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Ergonul
authors.forename: Frederic
authors.initials: F
authors.lastname: Clayton
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000911:Antibodies, Monoclonal; D002648:Child; D005260:Female; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D022622:Shiga Toxin 1 / Q000378:metabolism*; D013194:Staining and Labeling; D014281:Trihexosylceramides / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D006017:Glycolipids; D011956:Receptors, Cell Surface; D022622:Shiga Toxin 1; C068556:Shiga-like toxin receptor; D014281:Trihexosylceramides; C018549:globotriaosylceramide