title: Adiponectin diminishes organ-specific microvascular endothelial cell activation associated with sepsis.
abstract: Experimental sepsis was induced in male C57BL/6j, adiponectin-deficient mice (ADPNKO), and wild-type littermates by i.p. injection of 16 mg/kg lipopolysaccharide or cecal ligation and puncture. Blood and tissue samples were harvested 24 h after model induction. Circulating adiponectin is reduced in mice with endotoxemic challenge and after cecal ligation and puncture compared with healthy control mice. Quantitative reverse transcriptase-polymerase chain reaction for adiponectin reveals a pattern of response that is both model- and organ-specific. When challenged with sepsis, adiponectin deficiency results in increased expression of endothelial adhesion and coagulation molecules in the lung, liver, and kidney as quantified by reverse transcriptase-polymerase chain reaction, increased macrophage and neutrophil infiltration by immunohistochemistry, and vascular leakage in the liver and kidney. Adiponectin-deficient mice have reduced survival following cecal ligation and puncture and increased blood levels of interleukin 6, soluble vascular endothelial growth factor receptor 1, and soluble endothelial adhesion molecules E-selectin and intercellular adhesion molecule 1. Finally, ADPNKO promoted end-organ injury in the liver and kidney, whereas the lungs were not affected. These data suggest a protective role of adiponectin in diminishing microvascular organ-specific endothelial cell activation during sepsis.
authors.affiliation: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA. m.van.meurs@umcg.nl
authors.forename: Matijs
authors.initials: M
authors.lastname: van Meurs
authors.forename: Pedro
authors.initials: P
authors.lastname: Castro
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Shapiro
authors.forename: Shulin
authors.initials: S
authors.lastname: Lu
authors.forename: Midori
authors.initials: M
authors.lastname: Yano
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Jan G
authors.initials: JG
authors.lastname: Zijlstra
authors.forename: Grietje
authors.initials: G
authors.lastname: Molema
authors.forename: Samir M
authors.initials: SM
authors.lastname: Parikh
authors.forename: William C
authors.initials: WC
authors.lastname: Aird
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Yano
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000235:genetics; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055806:Microvessels / Q000166:cytology*; D018805:Sepsis / Q000097:blood* / Q000235:genetics / Q000378:metabolism* / Q000401:mortality
chemical_list: D052242:Adiponectin