title: Non-invasive optical imaging of eosinophilia during the course of an experimental allergic airways disease model and in response to therapy.
abstract: BACKGROUND
  Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils.
  
  
  RESULTS
  An ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h-72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs.
  
  
  CONCLUSIONS
  We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time.
authors.affiliation: Department of Haematology and Oncology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: M Andrea
authors.initials: MA
authors.lastname: Markus
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Dullin
authors.affiliation: Light Microscopy Facility, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Miso
authors.initials: M
authors.lastname: Mitkovski
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Prieschl-Grassauer
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Experimental Allergy, Medical University of Vienna, Vienna, Austria.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Epstein
authors.affiliation: Department of Haematology and Oncology, University Medical Center Göttingen, Göttingen, Germany ; Department of Molecular Biology of Neuronal Signals, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Alves
mesh_terms: D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001249:Asthma / Q000150:complications*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D004928:Escin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D061848:Optical Imaging; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D016896:Treatment Outcome
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C443130:Siglecf protein, mouse; D004928:Escin; D003907:Dexamethasone