title: Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism.
abstract: It is now well established that passive exposure to inhaled OVA leads to a state of immunological tolerance. Therefore, to elicit allergic sensitization, researchers have been compelled to devise alternative strategies, such as the systemic delivery of OVA in the context of powerful adjuvants, which are alien to the way humans are exposed and sensitized to allergens. The objectives of these studies were to investigate immune-inflammatory responses to intranasal delivery of a purified house dust mite (HDM) extract and to evaluate the role of GM-CSF in this process. HDM was delivered to BALB/c mice daily for 10 days. After the last exposure, mice were killed, bronchoalveolar lavage was performed, and samples were obtained. Expression/production of Th2-associated molecules in the lymph nodes, lung, and spleen were evaluated by real-time quantitative PCR and ELISA, respectively. Using this exposure protocol, exposure to HDM alone generated Th2 sensitization based on the expression/production of Th2 effector molecules and airway eosinophilic inflammation. Flow cytometric analysis demonstrated expansion and activation of APCs in the lung and an influx of activated Th2 effector cells. Moreover, this inflammation was accompanied by airways hyper-responsiveness and a robust memory-driven immune response. Finally, administration of anti-GM-CSF-neutralizing Abs markedly reduced immune-inflammatory responses in both lung and spleen. Thus, intranasal delivery of HDM results in Th2 sensitization and airway eosinophilic inflammation that appear to be mediated, at least in part, by endogenous GM-CSF production.
authors.affiliation: Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, Division of Respiratory Diseases and Allergy, McMaster University, 1200 Main Street, Hamilton, Ontario, Canada L8S 3Z5.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Cates
authors.forename: Ramzi
authors.initials: R
authors.lastname: Fattouh
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wattie
authors.forename: Mark D
authors.initials: MD
authors.lastname: Inman
authors.forename: Susanna
authors.initials: S
authors.lastname: Goncharova
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: José-Carlos
authors.initials: JC
authors.lastname: Gutierrez-Ramos
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D060829:Arthropod Proteins; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D004195:Disease Models, Animal; D004391:Dust / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007106:Immune Sera / Q000008:administration & dosage; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D004391:Dust; D007106:Immune Sera; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1