title: Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation.
abstract: BACKGROUND
  The calcium-binding protein S100A12 is highly up-regulated in the serum and sputum of patients with allergic asthma and is suggested to be a biomarker and pathologic mediator of asthma.
  
  
  OBJECTIVE
  To test the role of S100A12 in mediating airway inflammation in a mouse model of allergic lung inflammation.
  
  
  METHODS
  Transgenic (TG) mice that express human S100A12 and wild-type (WT) littermates were sensitized and challenged with ovalbumin (OVA) and assessed for inflammation, lung structure, and function.
  
  
  RESULTS
  Following OVA sensitization and challenge, S100A12 TG mice showed reduced peribronchial and perivascular inflammation, mucus production, and eosinophilia as well as attenuated airway responsiveness to contractile agonist compared with WT sensitized and challenged animals. This is explained, at least in part, by remodelled airways in S100A12 TG mice with thinning of the airway smooth muscle. S100A12 exposure induced Fas expression and activation of caspase 3 in cultured airway smooth muscle cells, suggesting that airway smooth muscle abnormalities observed in S100A12 TG mice may be mediated through myocyte apoptosis.
  
  
  CONCLUSIONS
  S100A12 is one of the most abundant proteins found in the airways of human asthmatics, and it was postulated that S100A12 could mediate the inflammatory process. Our study shows for the first time that TG expression of S100A12 in the lung of mice does not exacerbate lung inflammation in a model of OVA-induced allergic inflammation. We speculate that the high levels of S100/calgranulins found in bronchoalveolar lavage fluid of asthmatics and of OVA-treated TG S100A12 mice do not significantly mediate pulmonary inflammation.
authors.affiliation: Department of Medicine, Sections of Cardiology, The University of Chicago, Chicago, IL 60637, USA. mhofmann@medicine.BSD.uchicago.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Hofmann Bowman
authors.forename: A
authors.initials: A
authors.lastname: Heydemann
authors.forename: J
authors.initials: J
authors.lastname: Gawdzik
authors.forename: R A
authors.initials: RA
authors.lastname: Shilling
authors.forename: B
authors.initials: B
authors.lastname: Camoretti-Mercado
mesh_terms: D056151:Airway Remodeling / Q000235:genetics / Q000276:immunology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D056724:Immunity, Humoral / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D012137:Respiratory System / Q000276:immunology / Q000473:pathology; D009418:S100 Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000067616:S100A12 Protein
chemical_list: D018925:Chemokines; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D010047:Ovalbumin