Lipopolysaccharide upregulates renal shiga toxin receptors in a primate model of hemolytic uremic syndrome.

Abstract

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.

CONCLUSION:

These observations

• Authors: Frederic Clayton, Theodore J Pysher, Randall Lou, Donald E Kohan, Nathaniel D Denkers, Vernon L Tesh, Fletcher B Taylor Jr, Richard L Siegler
• Journal: American journal of nephrology (Am J Nephrol) 2005 Nov-Dec Vol. 25 Issue 6 Pg. 536-40 ISSN: 0250-8095 [Print] Switzerland
• PMID: 16179829 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• Shiga Toxin 1
• Trihexosylceramides
• globotriaosylceramide

Topics

• Animals
• Chromatography, Thin Layer
• Disease Models, Animal
• Hemolytic-Uremic Syndrome (metabolism, physiopathology)
• Kidney Cortex (chemistry, metabolism, physiopathology)
• Lipopolysaccharides (pharmacology)
• Microscopy, Fluorescence
• Shiga Toxin 1 (pharmacology)
• Trihexosylceramides (analysis, metabolism)
• Up-Regulation (drug effects)