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Abstract: TH-PO085

The Class B Scavenger Receptors BI and BII Exacerbate Acute Kidney and Liver Injury in Murine Abdominal Sepsis Model

Session Information

  • AKI: Mechanisms - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Hayase, Naoki, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Baranova, Irina, National Institutes of Health, Bethesda, Maryland, United States
  • Vishnyakova, Tatyana, National Institutes of Health, Bethesda, Maryland, United States
  • Bocharov, Alexander V., National Institutes of Health, Bethesda, Maryland, United States
  • Chari, Rohit R., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Aragao Carneiro dos Santos, Alef, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Hu, Xuzhen, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Yuen, Peter S.T., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Star, Robert A., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
Background

The class B scavenger receptors BI (SR-BI) and BII (SR-BII) are expressed in multiple tissues and known to recognize various pathogen-associated molecular patterns. Recently, we found that both receptors bind and internalize bacteria and boost proinflammatory cytokine production in HeLa cells transfected with SR-Bs. Moreover, we developed human SR-BI and BII transgenic mice (driven by pLiv-11) that overexpress hSR-BI and BII transgenes in the liver (to a lesser extent in the kidney). LPS I.P. injection markedly increases expression of proinflammatory cytokines in the liver and kidney of both transgenic mice. However, their roles in a clinically relevant sepsis model are unknown.

Methods

We performed cecum ligation and puncture (CLP) surgery in hSR-BI and BII transgenic and wild-type (WT) mice and treated them with antibiotics and fluids. A seven-day survival study was conducted. In a separate experiment at 24 h after CLP surgery, we collected blood, peritoneal lavage fluid, kidney, liver, and lungs for bacterial count, histological and biochemical examination.

Results

First, hSR-BI and BII transgenic mice had significantly worsened survival compared to WT mice (SR-BI vs. WT, 0.0% vs. 28.6% on Day 7, n = 5-7 per group, p = 0.002; SR-BII vs. WT, 0.0% vs. 28.6% on Day 7, n = 5-7 per group, p = 0.003). Second, the blood bacterial count was lower in both hSR-B transgenic mice than WT, while there was the similar trend in the number of bacteria in the peritoneal fluid. Alanine aminotransferase levels of hSR-BI and BII transgenic mice were significantly higher than WT. The kidneys of hSR-BI transgenic mice had abundant vacuole degeneration and the highest tubular injury score among the experimental groups.

Conclusion

In summary, our findings suggest that hSR-BI and BII overexpression contributes to higher mortality in the CLP sepsis by exacerbating liver and/or kidney injury. Future studies are planned (especially endocytosis of bacteria via the receptors, and production of proinflammatory cytokines) to further elucidate the pathogenetic roles of SR-BI/BII in a clinically translatable abdominal sepsis model.

Funding

  • NIDDK Support