Lipopolysaccharide upregulates renal shiga toxin receptors in a primate model of hemolytic uremic syndrome.
BACKGROUND
Although Shiga toxin (Stx) mediates classical hemolytic uremic syndrome (HUS), it is not fully understood why only some subjects exposed to Stx-expressing Escherichia coli develop HUS. We have previously shown in a baboon model of Stx-mediated HUS that coadministration of lipopolysaccharide (LPS) results in an augmented host response to otherwise subtoxic Stx1 doses. We used this model to test the hypothesis that LPS upregulates renal Stx receptor (Gb(3)) expression.


METHODS
Juvenile baboons were treated with either Stx1 (100 ng/kg), LPS (1 mg/kg as two divided doses 24 h apart), or a sham injection of saline, and sacrificed and immediately autopsied at 72 h. Renal cortical tissue Gb(3) content was quantitated by lipid extraction and thin-layer chromatography, and Stx1 and Gb(3)/CD77 immunostaining was assessed by quantitative immunofluorescent microscopy.


RESULTS
Compared to saline-injected controls, LPS administration resulted in a 2.2-fold increase in renal cortical Gb(3) by chromatography (p < 0.01), a 2.5-fold increase in Stx1 staining (p = 0.003) and a 1.7-fold increase in CD77 immunostaining (p = 0.004). Stx treatment did not significantly alter either Stx or CD77 immunostaining.


CONCLUSIONS
These observations
Clayton
Frederic
F
Department of Pathology, Salt Lake VA Medical Center, University of Utah School of Medicine, 50 N Medical Drive, Salt Lake City, 84132-2101, USA.
Pysher
Theodore J
TJ
Lou
Randall
R
Kohan
Donald E
DE
Denkers
Nathaniel D
ND
Tesh
Vernon L
VL
Taylor
Fletcher B
FB
Siegler
Richard L
RL
D000818:Animals; D002855:Chromatography, Thin Layer; D004195:Disease Models, Animal; D006463:Hemolytic-Uremic Syndrome / Q000378:metabolism* / Q000503:physiopathology; D007672:Kidney Cortex / Q000737:chemistry / Q000378:metabolism* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D022622:Shiga Toxin 1 / Q000494:pharmacology*; D014281:Trihexosylceramides / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D008070:Lipopolysaccharides; D022622:Shiga Toxin 1; D014281:Trihexosylceramides; C018549:globotriaosylceramide