Overproduction of acyloxyacyl hydrolase by macrophages and dendritic cells prevents prolonged reactions to bacterial lipopolysaccharide in vivo

Noredia Ojogun, Tang Yong Kuang, Baomei Shao, David R. Greaves, Robert S. Munford, Alan W. Varley

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Although recognition of lipopolysaccharide (LPS) by the myeloid differentiation factor 2-Toll-like receptor 4 complex is important for triggering protective inflammatory responses in animals, terminating many of these responses requires LPS inactivation by a host lipase, acyloxyacyl hydrolase (AOAH). To test whether endogenously produced recombinant AOAH can modulate responses to LPS and gram-negative bacteria, we engineered transgenic mice that overexpress AOAH in dendritic cells and macrophages, cell types that normally produce it. Transgenic mice deacylated LPS more rapidly than did wild-type controls. They also were protected from LPS-induced hepatosplenomegaly, recovered more quickly from LPS-induced weight loss, and were more likely to survive when challenged with live Escherichia coli. Constitutive overexpression of AOAH in vivo hastened recovery from LPS exposure without interfering with the normal acute inflammatory response to this important microbial signal molecule. Our results suggest that the extent to which macrophages and dendritic cells produce AOAH may influence the outcome of many gram-negative bacterial diseases.

Original languageEnglish (US)
Pages (from-to)1685-1693
Number of pages9
JournalJournal of Infectious Diseases
Volume200
Issue number11
DOIs
StatePublished - Nov 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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