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    Pleiotropic effects of angiopoietin-2 deficiency do not protect mice against endotoxin-induced acute kidney injury (2013)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Kurniati, Neng F
    van Meurs, Matijs
    vom Hagen, Franziska (WE 20)
    Jongman, Rianne M
    Moser, Jill
    Zwiers, Peter J
    Struys, Michel M R F
    Westra, Johanna
    Zijlstra, Jan G
    Hammes, Hans-Peter
    Molema, Grietje
    Heeringa, Peter
    Quelle
    Nephrology Dialysis Transplantation; 28(3) — S. 567–575
    ISSN: 0931-0509
    Sprache
    Englisch
    Verweise
    DOI: 10.1093/ndt/gfs336
    Pubmed: 22872727
    Kontakt
    Klinik für kleine Haustiere

    Oertzenweg 19 b
    Haus 1
    14163 Berlin
    +49 30 838 62356
    kleintierklinik@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    In sepsis and various other inflammatory conditions, elevated circulating levels of angiopoietin-2 (Ang2) are detected, but the precise functional role of Ang2 in these conditions is not well understood. Here, we investigated the contribution of Ang2 to the inflammatory response and renal function impairment in a mouse model of endotoxaemia.

    Ang2-deficient mice and wild-type littermates were challenged with lipopolysaccharide [LPS; 1500 EU/g, intraperitoneal (i.p.)]. In additional experiments, wild-type C57Bl/6 mice were depleted of circulating neutrophils by antibody treatment (NIMPR14) prior to LPS challenge to study the role of neutrophils in regulating LPS-induced cytokine release. After 8 or 24 h of LPS challenge, the mice were sacrificed and organs were harvested. Quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were performed for endothelial adhesion molecules (P-selectin, E-selectin, VCAM-1 and ICAM-1) and plasma cytokines (TNF-α, IL-6, KC, MIP-2), respectively. To assess renal function, blood urea nitrogen levels in plasma and albumin-to-creatinine ratio in urine were measured. RESULTS Upon LPS challenge, expression levels of various endothelial adhesion molecules in Ang2-deficient mice were reduced in an organ-specific manner. In contrast, in these mice, plasma levels of TNF-α and IL-6 were significantly increased compared with their wild-type littermates, possibly due to decreased neutrophil glomerular influx. Importantly, the absence of Ang2 did not protect the mice from acute kidney injury (AKI) upon LPS challenge. CONCLUSIONS The absence of Ang2 release upon LPS challenge induces pleotropic effects with regard to endothelial activation and systemic inflammation, but does not protect mice from LPS-induced AKI.