title: Allergen-induced murine upper airway inflammation: local and systemic changes in murine experimental allergic rhinitis.
abstract: The role of inflammatory effector cells in the pathogenesis of airway allergy has been the subject of much investigation. However, whether systemic factors are involved in the development of local responses in both upper and lower airways has not been fully clarified. The present study was performed to investigate aspects of the pathogenesis of isolated allergic rhinitis in a murine model sensitized to ovalbumin (OVA). Both upper- and lower-airway physiological responsiveness and inflammatory changes were assessed, as well as bone marrow progenitor responses, by culture and immunohistological methods. Significant nasal symptoms and hyper-responsiveness appeared after intranasal OVA challenge (P < 0.0001 and P < 0.01, respectively), accompanied with significant nasal mucosal changes in CD4+ cells (P < 0.001), interleukin (IL)-4+ cells (P < 0.01), IL-5+ cells (P < 0.01), basophilic cells (P < 0.02) and eosinophils (P < 0.001), in the complete absence of hyper-responsiveness or inflammatory changes in the lower airway. In the bone marrow, there were significant increases in CD34+ cells, as well as in eosinophils and basophilic cells. In the presence in vitro of mouse recombinant IL-5, IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF), the level of bone marrow eosinophil/basophil (Eo/Baso) colony-forming cells increased significantly in the OVA-sensitized group. We conclude that, in this murine model of allergic rhinitis, haemopoietic progenitors are upregulated, which is consistent with the involvement of bone marrow in the pathogenesis of nasal mucosal inflammation. Both local and systemic events, initiated in response to allergen provocation, may be required for the pathogenesis of allergic rhinitis. Understanding these events and their regulation could provide new therapeutic targets for rhinitis and asthma.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Howie
authors.forename: J
authors.initials: J
authors.lastname: Wattie
authors.forename: A
authors.initials: A
authors.lastname: Denburg
authors.forename: R
authors.initials: R
authors.lastname: Ellis
authors.forename: M D
authors.initials: MD
authors.lastname: Inman
authors.forename: J A
authors.initials: JA
authors.lastname: Denburg
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001491:Basophils / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D018929:Cell Culture Techniques; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology* / Q000473:pathology; D014343:Trypan Blue
chemical_list: D000485:Allergens; D007073:Immunoglobulin E; D010047:Ovalbumin; D014343:Trypan Blue