Septic shock is associated with receptor for advanced glycation end products ligation of LPS

Yasuhiko Yamamoto, Ai Harashima, Hidehito Saito, Koichi Tsuneyama, Seiichi Munesue, So Motoyoshi, Dong Han, Takuo Watanabe, Masahide Asano, Shin Takasawa, Hiroshi Okamoto, Satoshi Shimura, Tadahiro Karasawa, Hideto Yonekura, Hiroshi Yamamoto

Research output: Contribution to journalArticlepeer-review

120 Citations (Scopus)

Abstract

Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays a role in immune reactions to recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, the bioactive component of bacterial cell walls, and RAGE is unclear. In this study, we found direct LPS binding to RAGE by a surface plasmon resonance assay, a plate competition assay, and flow cytometry. LPS increased TNF-α secretion from peritoneal macrophages and an NF-κB promoter-driven luciferase activity through RAGE. Blood neutrophils and monocytes expressed RAGE, and TLR2 was counterregulated in RAGE-/- mice. After LPS injection, RAGE+/+ mice showed a higher mortality, higher serum levels of IL-6, TNF-α, high mobility group box 1, and endothelin-1, and severe lung and liver pathologies compared with RAGE-/- mice without significant differences in plasma LPS level. Administration of soluble RAGE significantly reduced the LPS-induced cytokine release and tissue damage and improved the LPS-induced lethality even in RAGE-/- as well as RAGE+/+ mice. The results thus suggest that RAGE can associate with LPS and that RAGE system can regulate inflammatory responses. Soluble RAGE would be a therapeutic tool for LPS-induced septic shock.

Original languageEnglish
Pages (from-to)3248-3257
Number of pages10
JournalJournal of Immunology
Volume186
Issue number5
DOIs
Publication statusPublished - 2011 Mar 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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