title: Vascular dysfunction following polymicrobial sepsis: role of pattern recognition receptors.
abstract: OBJECTIVE
  Aim was to elucidate the specific role of pattern recognition receptors in vascular dysfunction during polymicrobial sepsis (colon ascendens stent peritonitis, CASP).
  
  
  RESULTS
  Vascular contractility of C57BL/6 (wildtype) mice and mice deficient for Toll-like receptor 2/4/9 (TLR2-D, TLR4-D, TLR9-D) or CD14 (CD14-D) was measured 18 h following CASP. mRNA expression of pro- (Tumor Necrosis Factor-α (TNFα), Interleukin (IL)-1β, IL-6) and anti-inflammatory cytokines (IL-10) and of vascular inducible NO-Synthase (iNOS) was determined using RT-qPCR. Wildtype mice exhibited a significant loss of vascular contractility after CASP. This was aggravated in TLR2-D mice, blunted in TLR4-D animals and abolished in TLR9-D and CD14-D animals. TNF-α expression was significantly up-regulated after CASP in wildtype and TLR2-D animals, but not in mice deficient for TLR4, -9 or CD14. iNOS was significantly up-regulated in TLR2-D animals only. TLR2-D animals showed significantly higher levels of TLR4, -9 and CD14. Application of H154-ODN, a TLR9 antagonist, attenuated CASP-induced cytokine release and vascular dysfunction in wildtype mice.
  
  
  CONCLUSIONS
  Within our model, CD14 and TLR9 play a decisive role for the development of vascular dysfunction and thus can be effectively antagonized using H154-ODN. TLR2-D animals are more prone to polymicrobial sepsis, presumably due to up-regulation of TLR4, 9 and CD14.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Stefan Felix
authors.initials: SF
authors.lastname: Ehrentraut
authors.forename: Anne
authors.initials: A
authors.lastname: Dörr
authors.forename: Heidi
authors.initials: H
authors.lastname: Ehrentraut
authors.forename: Ralph
authors.initials: R
authors.lastname: Lohner
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeft
authors.forename: Georg
authors.initials: G
authors.lastname: Baumgarten
authors.forename: Pascal
authors.initials: P
authors.lastname: Knuefermann
authors.forename: Olaf
authors.initials: O
authors.lastname: Boehm
authors.forename: Rainer
authors.initials: R
authors.lastname: Meyer
mesh_terms: D000818:Animals; D060085:Coinfection / Q000150:complications / Q000382:microbiology*; D015169:Colony Count, Microbial; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications / Q000382:microbiology*; D051193:Toll-Like Receptors / Q000235:genetics; D014652:Vascular Diseases / Q000209:etiology* / Q000503:physiopathology
chemical_list: D018950:Lipopolysaccharide Receptors; D051193:Toll-Like Receptors