title: Organ-specific monocyte activation in necrotizing pancreatitis in mice.
abstract: BACKGROUND
  Acute necrotizing pancreatitis (NAP) induces a systemic inflammatory response syndrome. We investigated the underlying changes of monocytes using different activation markers.
  
  
  METHODS
  A retrograde injection of 2 mL/kg bodyweight of sodium taurocholate into the common bile duct of BALB/c mice induced NAP, whereas sham-operated animals (SOP) were treated with saline. After 6, 12, 24, and 48 h, histologic alterations, pancreatic enzymes, and interleukin 6 in serum, albumin, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid were examined. Isolation of mononuclear cells from the blood, spleen, and liver and the subsequent determination of macrophages (F4/80) and their activation marker CD121b and MHCII (1Ad) were performed by fluorescence-activated cell sorting (FACS analyses).
  
  
  RESULTS
  After pancreatitis induction, pancreatic enzymes (amylase: SOP 7008 U/L, NAP 37,044 U/L, P < 0.001) and histologic pancreatic damage (SOP 0.80 ± 1.92, NAP 19.6 ± 0.64, P < 0.001) developed instantly. Pulmonary vascular damage and MPO were detected between 6 and 12 h after onset (6 h albumin SOP 132.0 ± 12.0 μg/mL, NAP 267.2 ± 49.6 μg/mL; P < 0.05; MPO SOP 0.23 ± 0.20 ng/mL, NAP 11.29 ± 3.12 ng/mL, P < 0.01). Blood levels of interleukin 6 increased after 12-24 h (12 h SOP 584 ± 300 pg/mL; NAP 2169 ± 942 pg/mL, P < 0.05), whereas monocytes increased fourfold within 48 h (P < 0.05). Furthermore, pancreatitis increased the percentage of activated monocytes in the blood (6 h and/or 48 h: MHCII (1Ad) 2196%/5.65%; CD121b 51,654%/82,146%). Similar observations were made for monocytes from the liver and spleen.
  
  
  CONCLUSIONS
  Although inflammatory mediators increased during 24 h after pancreatitis induction, monocyte activation lasted for at least 48 h. The latter is not limited to blood but also detected in isolated liver and spleen monocytes.
authors.affiliation: Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
authors.forename: Andrea I
authors.initials: AI
authors.lastname: Schmidt
authors.affiliation: Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Seifert
authors.affiliation: Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Lauch
authors.affiliation: Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Wolff-Vorbeck
authors.affiliation: Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Chikhladze
authors.affiliation: Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
authors.forename: Ulrich T
authors.initials: UT
authors.lastname: Hopt
authors.affiliation: Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany. Electronic address: uwe.wittel@uniklinik-freiburg.de.
authors.forename: Uwe A
authors.initials: UA
authors.lastname: Wittel
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005434:Flow Cytometry; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016215:Macrophage-Activating Factors
keywords: Activation; Acute necrotizing pancreatitis; Macrophages; SIRS