Deletion of scavenger receptor A gene in mice resulted in protection from septic shock and modulation of TLR4 signaling in isolated peritoneal macrophages

Robert Drummond, David M. Cauvi, Dennis Hawisher, Donghuan Song, Diego F. Niño, Raul Coimbra, Stephen Bickler, Antonio De Maio

Research output: Contribution to journalArticlepeer-review

Abstract

Scavenger receptor A (Sra), also known as macrophage scavenger receptor 1 (Msr1), is a surface glycoprotein preferentially present in macrophages that plays a primary role in innate immunity. Previous studies have shown that Sra is a modifier gene for the response to bacterial LPS in mice at the level of IL-10 production, in particular. In the present study, we found that Sra(-/-) mice are more resistant to septic shock induced by cecal ligation and puncture than wild-type C57BL/6 J (B6) mice. In addition, Sra(-/-) mice displayed initial elevated high density lipoprotein (HDL) circulating levels. Naïve peritoneal macrophages (PMφs) were isolated from Sra(-/-) mice to understand the possible protective mechanism. Incubation of these cells with LPS was found to modulate TLR4 signaling, leading to a reduction in IL-10 and IL-6 mRNA levels, but not TNF-α expression, at low concentrations of LPS in comparison with PMφs isolated from B6 mice. No differences were found in LPS binding between PMφs derived from Sra(-/-) or B6 mice. The lack of Sra binding to LPS was confirmed after transfection of Chinese hamster ovary (CHO) cells with the Sra gene. The contribution of Sra to the outcome of sepsis may be a combination of changes in TLR4 signaling pathway and elevated levels of HDL in circulation, but also LPS toxicity.

Original languageEnglish (US)
Pages (from-to)30-41
Number of pages12
JournalInnate Immunity
Volume19
Issue number1
DOIs
StatePublished - Feb 2013

Keywords

  • Cholesterol
  • HDL
  • cytokines
  • inflammation
  • lipopolysaccharide
  • macrophage
  • sepsis
  • toll-like receptor

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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