Abstract
Induction of experimental hemolytic uremic syndrome (HUS) by simply administering Shiga-like toxin (Stx) to rodents has not yet been successful. Attention has been paid to the role of lipopolysaccharide (LPS) in the pathogenesis of HUS. In this study, we showed successful induction of an experimental HUS in LPS responder mice by administering Stx together with LPS. Intraperitoneal administration of 200 ng of Stx 2 for 2 days, followed by 250 μg of LPS on the 2nd day of Stx administration, caused a significant decrease of thrombocytes and deterioration of renal function, with proteinuria and hematuria. Electron microscopy revealed alterations of glomerular endothelial cells. Administration of Stx alone or LPS alone caused neither hematological nor histopathological changes, as were observed with Stx and LPS co-administration. Interestingly, when LPS was administered before Stx, no hematological and histological changes were observed. The results showed that LPS was essential for the induction of HUS, but LPS pretreatment might protect against Stx toxicity. The order of LPS and Stx administration is important for the induction of experimental HUS.
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Acknowledgements
Stx2 was graciously provided by Dr. Kohsaka (Department of Pediatric Nephrology, National Children’s Hospital, Tokyo, Japan). The authors thank Mr. Hoshino and Mr. Takahashi for their laboratory assistance. This work was supported by a grant for “EHEC associated hemolytic uremic syndrome” from the Ministry of Health and Welfare project for “A newly risen and revived infectious disease”.
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Ikeda, M., Ito, S. & Honda, M. Hemolytic uremic syndrome induced by lipopolysaccharide and Shiga-like toxin. Pediatr Nephrol 19, 485–489 (2004). https://doi.org/10.1007/s00467-003-1395-7
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DOI: https://doi.org/10.1007/s00467-003-1395-7