Scavenger receptor BI protects against septic death through its role in modulating inflammatory response

Ling Guo, Zhiqing Song, Mengting Li, Qingan Wu, Dan Wang, Hong Feng, Philip Bernard, Alan Daugherty, Bin Huang, Xiang An Li

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Sepsis is a leading cause of death that is characterized by uncontrolled inflammatory response. In this study, we report that scavenger receptor BI (SR-131), a high density lipoprotein receptor, ig a critical survival factor of sepsis. We induced sepsis using an established septic animal model, cecal ligation and puncture (CLP). CLP induced 100% fatality in SR-BI-null mice but only 21% fatality in wild type littermates. SR-BI-null mice exhibited aberrant inflammatory responses with delayed inflammatory cytokine generation at the early stage of sepsis and highly elevated inflammatory cytokine production 20 h after CLP treatment. To understand the mechanisms underlying SR-BI protection, we elucidated the effect of macrophage SR-BI on inflammatory cytokine generation. Macrophages from SR-BI-null mice produced significantly higher levels of inflammatory cytokines than those of wild type controls in response to LPS. Importantly, transgenic mice overexpressing SR-BI were more resistant to CLP-induced septic death. Using an HEK-Blue™ cell system, we demonstrated that expression of SR-BI suppressed TLR4-mediated NF-κB activation. To understand why SR-BI-null mice had a delayed inflammatory response, we elucidated the effect of SR-BI on LPS clearance during sepsis. Compared with wild type controls, SR-BI-null mice had lower plasma LPS levels in the early stage of sepsis and elevated plasma LPS levels 20 h following CLP treatment. In conclusion, our findings demonstrate that SR-BI is a critical protective modulator of sepsis in mice. SR-BI exerts its protective function through its role in modulating inflammatory response in macrophages and facilitating LPS recruitment and clearance.

Original languageEnglish
Pages (from-to)19826-19834
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number30
DOIs
StatePublished - Jul 24 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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