title: Evaluation of arginine metabolism for the analysis of M1/M2 macrophage activation in human clinical specimens.
abstract: BACKGROUND
  Macrophage heterogeneity reflects their plasticity in response to environmental stimuli. Usually human macrophages are characterized by analysis of surface molecules or cytokine expression while functional assays are established in the mouse system but lacking for various human specimens.
  
  
  METHODS
  To evaluate the value of analysis of arginine metabolism for characterization of human macrophage differentiation, we analyzed nitrite production and arginase activity in plasma, duodenal biopsies, and in vitro differentiated macrophages of patients with classical Whipple's disease.
  
  
  RESULTS
  We demonstrate that it is feasible to determine the content of urea in supernatants of stimulated duodenal biopsies, arginase activity in fresh duodenal biopsies and plasma samples, and arginase activity and nitrite production in lysates and supernatants of in vitro differentiated macrophages. However, only selected tests are appropriate to define macrophage polarization in human specimens.
  
  
  CONCLUSIONS
  Analysis of arginine metabolism is not suitable for the characterization of in vitro differentiated human macrophages. Besides the measurement of nitrite in duodenal biopsy supernatants, the determination of arginase activity in human plasma seems to be a reasonable functional test to detect enhanced M2 macrophage activation and, thus, is of great value for the analysis of macrophage activity with a minimum of material and costs.
authors.affiliation: Campus Benjamin Franklin, Medizinische Klinik I, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Geelhaar-Karsch
authors.forename: Katina
authors.initials: K
authors.lastname: Schinnerling
authors.forename: Kristina
authors.initials: K
authors.lastname: Conrad
authors.forename: Julian
authors.initials: J
authors.lastname: Friebel
authors.forename: Kristina
authors.initials: K
authors.lastname: Allers
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
authors.forename: Verena
authors.initials: V
authors.lastname: Moos
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D002454:Cell Differentiation; D003955:Diagnostic Tests, Routine / Q000379:methods*; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009573:Nitrites / Q000378:metabolism; D011237:Predictive Value of Tests; D008061:Whipple Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D009573:Nitrites; D001120:Arginine