Abstract: TH-PO0112
Human Scavenger Receptors BI and BII Overexpressed in Murine Abdominal Sepsis Model
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Hayase, Naoki, 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
- Hu, Xuzhen, National Institutes of Health, Bethesda, Maryland, United States
- Yuen, Peter S.T., National Institutes of Health, Bethesda, Maryland, United States
- Star, Robert A., National Institutes of Health, Bethesda, Maryland, United States
Background
Class B scavenger receptors BI (SR-BI) and BII (SR-BII) can bind and internalize lipoproteins and bacteria (our recent work in vitro). However, their roles in vivo in a clinically relevant sepsis model are unknown.
Methods
We overexpressed human SR-BI and BII (driven by pLiv-11) in the liver and to a lesser extent in the kidney. We performed cecum ligation and puncture (CLP)-induced sepsis surgery, and followed mice for a 7 d-survival study. We also collected blood, peritoneal lavage fluid, kidney, and liver for organ-specific assessment 24 h after CLP surgery. To examine intracellular translocation of bacteria, we infected mouse primary hepatocytes and proximal tubular cells with Escherichia Coli K 12. Intracellular bacteria were counted. To examine in vivobacterial accumulation, GFP-labeled E. coli was intravenously injected to hSR-BI and BII transgenic and WT mice. Isolated liver, kidney, and adrenal gland were observed under a confocal microscope.
Results
hSR-BI and BII transgenic mice had significantly worse survival compared to WT mice (SR-BI vs. WT, 6.3% vs. 33.3%, p = 0.001; SR-BII vs. WT, 6.3% vs. 33.3%, p = 0.001). 24 h after CLP, liver organ injury markers and histological injury score were significantly higher in hSR-B transgenic than WT mice, while the extent of kidney injury was comparable between hSR-B transgenic and WT mice. Systemic inflammatory cytokines were markedly increased in hSR-B transgenic mice; parallel increases were seen in liver mRNA expression, not in kidney. Glucocorticoid production was suppressed, and lipid droplets were diminished in the adrenal cortex of hSR-B transgenic mice. We found more intracellular bacteria inside primary cultured hepatocytes from hSR-B transgenic than WT mice, while the bacterial internalization in kidney of hSR-B transgenic mice was as modest as WT mice. Injection of GFP-labeled E. coli revealed more accumulation of GFP-labeled E. coli in liver parenchyma of SR-B transgenic than WT mice.
Conclusion
In summary, our findings suggest hSR-BI and BII overexpression contributes to higher mortality in CLP sepsis by adrenal insufficiency, systemic hyperinflammation, and bacterial invasion in liver. Class B scavenger receptors (SR-BI and SR-BII) may play pivotal roles in corticosterone production, innate immunity, and internalization of bacteria during sepsis.
Funding
- NIDDK Support