Involvement of high mobility group box 1 in the pathogenesis of severe hemolytic uremic syndrome in a murine model.

Abstract

Typical hemolytic uremic syndrome is caused by Shiga toxin (Stx2) and lipopolysaccharide (LPS) of Escherichia coli and leads to acute kidney injury. The role of innate immunity in this pathogenesis is unclear. We analyzed the role of high mobility group box 1 (HMGB1) at the onset of disease in a murine model. C57BL/6 mice were intraperitoneally administered saline (group A), anti-HMGB1 monoclonal antibody (group B), Stx2 and LPS to elicit severe disease (group C), or Stx2, LPS, and anti-HMGB1 antibody (group D). While all mice in group C died by day 5 of the experiment, all mice in group D survived. Anemia and thrombocytopenia were pronounced and plasma creatinine levels were significantly elevated in group C only at 72 h. While at 72 h after toxin administration the glomerulus tissue in group C showed pathology similar to that of humans, mesangial cell proliferation was seen in group D. Plasma HMGB1 levels in group C peaked 3 h after administration and were higher than those in other groups. Expression of the receptor of advanced glycation end products and NF-κB, involved in HMGB1 signaling, was significantly elevated in group C but not in group D. Administration of anti-HMGB1 antibody in a murine model of severe disease inhibited plasma HMGB1 and promoted amelioration of tissue damage. HMGB1 was found to be involved in the disease pathology; therefore, controlling HMGB1 activity might inhibit disease progression.

• Authors: Ryo Maeda, Yukihiko Kawasaki, Yohei Kume, Hayato Go, Kazuhide Suyama, Mitsuaki Hosoya
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 317 Issue 6 Pg. F1420-F1429 (12 01 2019) ISSN: 1522-1466 [Electronic] United States
• PMID: 31482731 (Publication Type: Journal Article)

Chemical References

• Antibodies, Blocking
• Cytokines
• Glycation End Products, Advanced
• HMGB1 Protein
• HMGB1 protein, mouse
• Lipopolysaccharides
• NF-kappa B
• Syntaxin 1
• Creatinine

Topics

• Anemia (etiology)
• Animals
• Antibodies, Blocking
• Creatinine (blood)
• Cytokines (analysis, metabolism)
• Glycation End Products, Advanced (metabolism)
• HMGB1 Protein (antagonists & inhibitors, genetics, immunology)
• Hemolytic-Uremic Syndrome (chemically induced, genetics, pathology)
• Kidney Glomerulus (pathology)
• Lipopolysaccharides
• Male
• Mesangial Cells (pathology)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Survival Analysis
• Syntaxin 1 (metabolism)
• Thrombocytopenia (etiology)