Mouse model of hemolytic-uremic syndrome caused by endotoxin-free Shiga toxin 2 (Stx2) and protection from lethal outcome by anti-Stx2 antibody

Kristin A D Sauter, Angela R. Melton-Celsa, Kay Larkin, Megan Troxell, Alison D. O'Brien, Bruce E. Magun

Research output: Contribution to journalArticle

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Abstract

Hemolytic-uremic syndrome (HUS) results from infection by Shiga toxin (Stx)-producing Escherichia coli and is the most common cause of acute renal failure in children. We have developed a mouse model of HUS by administering endotoxin-free Stx2 in multiple doses over 7 to 8 days. At sacrifice, moribund animals demonstrated signs of HUS: increased blood urea nitrogen and serum creatinine levels, proteinuria, deposition of fibrin(ogen), glomerular endothelial damage, hemolysis, leukocytopenia, and neutrophilia. Increased expression of proinflammatory chemokines and cytokines in the sera of Stx2-treated mice indicated a systemic inflammatory response. Currently, specific therapeutics for HUS are lacking, and therapy for patients is primarily supportive. Mice that received 11E10, a monoclonal anti-Stx2 antibody, 4 days after starting injections of Stx2 recovered fully, displaying normal renal function and normal levels of neutrophils and lymphocytes. In addition, these mice showed decreased fibrin(ogen) deposition and expression of proinflammatory mediators compared to those of Stx2-treated mice in the absence of antibody. These results indicate that, when performed during progression of HUS, passive immunization of mice with anti-Stx2 antibody prevented the lethal effects of Stx2.

Original languageEnglish (US)
Pages (from-to)4469-4478
Number of pages10
JournalInfection and Immunity
Volume76
Issue number10
DOIs
StatePublished - Oct 2008

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Shiga Toxin 2
Hemolytic-Uremic Syndrome
Endotoxins
Antibodies
Fibrin
Shiga-Toxigenic Escherichia coli
Passive Immunization
Blood Urea Nitrogen
Leukopenia
Hemolysis
Serum
Proteinuria
Chemokines
Acute Kidney Injury
Creatinine
Neutrophils
Lymphocytes
Cytokines
Kidney
Injections

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Mouse model of hemolytic-uremic syndrome caused by endotoxin-free Shiga toxin 2 (Stx2) and protection from lethal outcome by anti-Stx2 antibody. / Sauter, Kristin A D; Melton-Celsa, Angela R.; Larkin, Kay; Troxell, Megan; O'Brien, Alison D.; Magun, Bruce E.

In: Infection and Immunity, Vol. 76, No. 10, 10.2008, p. 4469-4478.

Research output: Contribution to journalArticle

Sauter, Kristin A D ; Melton-Celsa, Angela R. ; Larkin, Kay ; Troxell, Megan ; O'Brien, Alison D. ; Magun, Bruce E. / Mouse model of hemolytic-uremic syndrome caused by endotoxin-free Shiga toxin 2 (Stx2) and protection from lethal outcome by anti-Stx2 antibody. In: Infection and Immunity. 2008 ; Vol. 76, No. 10. pp. 4469-4478.
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