Non-invasive optical imaging of eosinophilia during the course of an experimental allergic airways disease model and in response to therapy

PLoS One. 2014 Feb 25;9(2):e90017. doi: 10.1371/journal.pone.0090017. eCollection 2014.

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.

Methodology/principal findings: 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.

Conclusion/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Asthma / complications*
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Eosinophilia / complications
  • Eosinophilia / diagnosis*
  • Eosinophilia / drug therapy*
  • Eosinophilia / metabolism
  • Escin / pharmacology
  • Escin / therapeutic use
  • Female
  • Gene Expression Regulation / drug effects
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Optical Imaging*
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Treatment Outcome

Substances

  • Antigens, Differentiation, Myelomonocytic
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Siglecf protein, mouse
  • Escin
  • Dexamethasone

Grants and funding

The presented data is part of the P3AGI project (public private partnership for asthma imaging and genomics) funded by the European Commission through an FP7- IAPP Marie Curie Action (GA 230739). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.