title: Monocytes with angiogenic potential are selectively induced by liver resection and accumulate near the site of liver regeneration.
abstract: BACKGROUND
  Monocytes reportedly contribute to liver regeneration. Three subsets have been identified to date: classical, intermediate, non-classical monocytes. The intermediate population and a subtype expressing TIE2 (TEMs) were suggested to promote angiogenesis. In a clinical setting, we investigated which monocyte subsets are regulated after liver resection and correlate with postoperative liver function.
  
  
  METHODS
  In 38 patients monocyte subsets were evaluated in blood and subhepatic wound fluid by flow cytometry before and 1-3 days after resection of colorectal liver metastases. The monocyte-regulating cytokines macrophage colony stimulating factor (M-CSF), transforming growth factor beta 1 (TGFβ1), and angiopoietin 2 (ANG-2) were measured in patient plasma by ELISA. C-reactive protein (CRP) and liver function parameters were retrieved from routine hospital analyses.
  
  
  RESULTS
  On post-operative day (POD) 1 blood monocytes shifted to significantly elevated levels of intermediate monocytes. In wound fluid, a delayed surge in intermediate monocytes was detected by POD 3. Furthermore, TEMs were highly enriched in wound fluid as compared to circulation. CRP and M-CSF levels were substantially increased in patient blood after surgery and correlated significantly with the frequency of intermediate monocytes. In addition, liver function parameters showed a significant association with intermediate monocyte levels on POD 3.
  
  
  CONCLUSIONS
  The reportedly pro-angiogenic subsets of monocytes are selectively increased upon liver resection and accumulate next to the site of liver regeneration. As previously proposed by in vitro experiments, the release of CRP and M-CSF may trigger the induction of intermediate monocytes. The correlation with liver parameters points to a functional involvement of these monocyte populations in liver regeneration which warrants further investigation.
authors.forename: Dominic
authors.initials: D
authors.lastname: Schauer
authors.forename: Patrick
authors.initials: P
authors.lastname: Starlinger
authors.forename: Philipp
authors.initials: P
authors.lastname: Zajc
authors.forename: Lejla
authors.initials: L
authors.lastname: Alidzanovic
authors.forename: Thomas
authors.initials: T
authors.lastname: Maier
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Buchberger
authors.forename: Lorand
authors.initials: L
authors.lastname: Pop
authors.forename: Birgit
authors.initials: B
authors.lastname: Gruenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Gruenberger
authors.forename: Christine
authors.initials: C
authors.lastname: Brostjan
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003710:Demography; D005260:Female; D006801:Humans; D008099:Liver / Q000601:surgery*; D008115:Liver Regeneration; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D019990:Perioperative Care; D011184:Postoperative Period; D042787:Receptor, TIE-2 / Q000378:metabolism
chemical_list: D016207:Cytokines; D016173:Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; D042787:Receptor, TIE-2