title: Hepatocyte-specific S100a8 and S100a9 transgene expression in mice causes Cxcl1 induction and systemic neutrophil enrichment.
abstract: BACKGROUND
  Calprotectin consists of the Ca2+-binding proteins S100a8 and S100a9 that are induced in epithelial cells in response to tissue damage and infection. Both proteins are also secreted by activated innate immune cells and numerous studies demonstrate their crucial role in pathological conditions of acute and chronic inflammation.
  
  
  RESULTS
  Here, we established a conditional mouse model with simultaneous S100a8 and S100a9 transgene expression in hepatocytes (TgS100a8a9hep) under the control of doxycycline to unravel the role of epithelial-derived Calprotectin on tissue homeostasis and inflammation. TgS100a8a9hep mice displayed a significant enrichment of neutrophils in peripheral blood and tissues with high blood content. Interestingly, Cxcl1 transcription was significantly induced in the liver of TgS100a8a9hep mice and primary hepatocytes derived thereof as compared to Control mice, accompanied by an increase of Cxcl1 serum levels. However, expression of other chemokines with a known function in neutrophil mobilization from the bone marrow, e.g. Csf3 and Cxcl2, was not altered. Doxycycline treatment of TgS100a8a9hep mice reduced Cxcl1 expression in the liver and resulted in normal numbers of neutrophils.
  
  
  CONCLUSIONS
  In summary, our data demonstrate for the first time that hepatocyte-specific S100a8 and S100a9 expression induces a systemic mobilization of neutrophils by a specific activation of Cxcl1 transcription in the liver.
authors.affiliation: Junior Group Molecular Mechanisms of Head and Neck Tumors, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany. j.hess@dkfz-heidelberg.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Wiechert
authors.forename: Julia
authors.initials: J
authors.lastname: Németh
authors.forename: Tobias
authors.initials: T
authors.lastname: Pusterla
authors.forename: Christine
authors.initials: C
authors.lastname: Bauer
authors.forename: Aurora
authors.initials: A
authors.lastname: De Ponti
authors.forename: Sandra
authors.initials: S
authors.lastname: Manthey
authors.forename: Silke
authors.initials: S
authors.lastname: Marhenke
authors.forename: Arndt
authors.initials: A
authors.lastname: Vogel
authors.forename: Ursula
authors.initials: U
authors.lastname: Klingmüller
authors.forename: Jochen
authors.initials: J
authors.lastname: Hess
authors.forename: Peter
authors.initials: P
authors.lastname: Angel