title: Lung-homing of endothelial progenitor cells and airway vascularization is only partially dependant on eosinophils in a house dust mite-exposed mouse model of allergic asthma.
abstract: BACKGROUND
  Asthmatic responses involve a systemic component where activation of the bone marrow leads to mobilization and lung-homing of progenitor cells. This traffic may be driven by stromal cell derived factor-1 (SDF-1), a potent progenitor chemoattractant. We have previously shown that airway angiogenesis, an early remodeling event, can be inhibited by preventing the migration of endothelial progenitor cells (EPC) to the lungs. Given intranasally, AMD3100, a CXCR4 antagonist that inhibits SDF-1 mediated effects, attenuated allergen-induced lung-homing of EPC, vascularization of pulmonary tissue, airway eosinophilia and development of airway hyperresponsiveness. Since SDF-1 is also an eosinophil chemoattractant, we investigated, using a transgenic eosinophil deficient mouse strain (PHIL) whether EPC lung accumulation and lung vascularization in allergic airway responses is dependent on eosinophilic inflammation.
  
  
  METHODS
  Wild-type (WT) BALB/c and eosinophil deficient (PHIL) mice were sensitized to house dust mite (HDM) using a chronic exposure protocol and treated with AMD3100 to modulate SDF-1 stimulated progenitor traffic. Following HDM challenge, lung-extracted EPCs were enumerated along with airway inflammation, microvessel density (MVD) and airway methacholine responsiveness (AHR).
  
  
  RESULTS
  Following Ag sensitization, both WT and PHIL mice exhibited HDM-induced increase in airway inflammation, EPC lung-accumulation, lung angiogenesis and AHR. Treatment with AMD3100 significantly attenuated outcome measures in both groups of mice. Significantly lower levels of EPC and a trend for lower vascularization were detected in PHIL versus WT mice.
  
  
  CONCLUSIONS
  This study shows that while allergen-induced lung-homing of endothelial progenitor cells, increased tissue vascularization and development lung dysfunction can occur in the absence of eosinophils, the presence of these cells worsens the pathology of the allergic response.
authors.affiliation: Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Nirooya
authors.initials: N
authors.lastname: Sivapalan
authors.affiliation: Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wattie
authors.affiliation: Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Inman
authors.affiliation: Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology*
chemical_list: D000485:Allergens