Compartmentalized transgene expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mouse lung enhances allergic airways inflammation
| Autor: | Manel Jordana, J Gauldie, Y Ohkawara, Martin R. Stämpfli, Zhou Xing, X.-F. Lei, Kenneth Croitoru |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Ovalbumin
Transgene medicine.medical_treatment Genetic Vectors Immunology Apoptosis Inflammation Adenoviridae Mice medicine Animals Immunology and Allergy Eosinophilia Transgenes Lung Mice Inbred BALB C medicine.diagnostic_test biology Genetic transfer Granulocyte-Macrophage Colony-Stimulating Factor Epithelial Cells respiratory system Eosinophil Asthma respiratory tract diseases Bronchoalveolar lavage medicine.anatomical_structure Cytokine Gene Targeting biology.protein Original Article Female Interleukin-4 Interleukin-5 medicine.symptom Bronchoalveolar Lavage Fluid |
| Zdroj: | Clinical and Experimental Immunology. 113:157-165 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1046/j.1365-2249.1998.00652.x |
| Popis: | SUMMARYTo investigate the role of GM-CSF in asthmatic airways inflammation, we have targeted GM-CSF transgene to the airway cells in a mouse model of ovalbumin (OVA)-induced allergic airways inflammation, a model in which there is marked induction of endogenous IL-5 and IL-4 but not GM-CSF. Following intranasal delivery of a replication-deficient adenoviral gene transfer vector (Ad), transgene expression was found localized primarily to the respiratory epithelial cells. Intranasal delivery of 0.03 × 109 plaque-forming units (PFU) of AdGM-CSF into naive BALB/c mice resulted in prolonged and compartmentalized release of GM-CSF transgene protein with a peak concentration of ≈ 80 pg/ml detected in bronchoalveolar lavage fluid (BALF) at day 7, but little in serum. These levels of local GM-CSF expression per se resulted in no eosinophilia and only a minimum of tissue inflammatory responses in the lung of naive mice, similar to those induced by the control vector. However, such GM-CSF expression in the airways of OVA-sensitized mice resulted in a much greater and sustained accumulation of various inflammatory cell types, most noticeably eosinophils, both in BALF and airway tissues for 15–21 days post-OVA aerosol challenge, at which times airways inflammation had largely resolved in control mice. While the levels of IL-5 and IL-4 in BALF and the rate of eosinophil apoptosis were found similar between different treatments, there was an increased number of proliferative leucocytes in the lung receiving GM-CSF gene transfer. Our results thus provide direct experimental evidence that GM-CSF can significantly contribute to the development of allergic airways inflammation through potentiating and prolonging inflammatory infiltration induced by cytokines such as IL-5 and IL-4. |
| Databáze: | OpenAIRE |
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