title: Systemic and intestinal levels of factor XIII-A: the impact of inflammation on expression in macrophage subtypes.
abstract: BACKGROUND
  Subunit A of coagulation factor XIII (FXIII-A) is important for clot stability and acts in the subsequent wound healing process. Loss of plasma FXIII-A has been reported after surgery, sepsis, and inflammatory conditions. In the intestinal mucosa, FXIII-A is expressed by macrophages and cellular FXIII-A has been associated with phagocytosis and migration of macrophages. The objective was to evaluate the consequences of intestinal inflammation on resident mucosal macrophages, focusing on the level and distribution of FXIII-A.
  
  
  METHODS
  Plasma and colonic biopsies were collected from 67 patients with ulcerative colitis and controls. Intestinal samples were stained using immunohistochemistry for FXIII-A and macrophages (CD68, CD163 and iNOS). In situ hybridization were used to assess the intestinal expression of FXIII-A. FXIII-A antigen and activity levels were measured in plasma.
  
  
  RESULTS
  Increased infiltration of CD68 positive macrophages in the inflamed mucosa coincided with increased extracellular deposited FXIII-A and decreased expression and intracellular protein levels of FXIII-A. A decreased proportion of FXIII-A/CD68/CD163 triple-positive macrophages was observed in inflamed mucosa, indicating a reduction of the M2 phenotype with consequent loss of FXIII-A. No induction of iNOS positive macrophages was observed. Stimulation of naïve monocytes with physiological concentrations of pro-inflammatory mediators negatively affected the expression of FXIII-A. Measurements in plasma confirmed the loss of both FXIII antigen and activity during active disease.
  
  
  CONCLUSIONS
  Intestinal inflammation in UC induces loss of M2 macrophages with subsequent loss of FXIII-A synthesis. The loss of cellular FXIII-A may impact migration and phagocytosis, and hence limit pathogen eradication in UC.
authors.affiliation: Department of Gastroenterology 54O3, Medical Section, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark. christoffer.soendergaard@regionh.dk.|Department of Histology and Bioimaging, Novo Nordisk A/S, Maaloev, Denmark. christoffer.soendergaard@regionh.dk.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Soendergaard
authors.affiliation: Department of Histology and Bioimaging, Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: Peter Helding
authors.initials: PH
authors.lastname: Kvist
authors.affiliation: Department of Gastroenterology 54O3, Medical Section, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark.
authors.forename: Jakob Benedict
authors.initials: JB
authors.lastname: Seidelin
authors.affiliation: Department of Research Bioanalysis, Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: Hermann
authors.initials: H
authors.lastname: Pelzer
authors.affiliation: Department of Gastroenterology 54O3, Medical Section, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark.
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D026122:Factor XIIIa / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D026122:Factor XIIIa
keywords: Factor XIII; Immunohistochemistry; In situ hybridization; Inflammation; Macrophages; Ulcerative colitis