- Title
- Granulocyte-macrophage colony-stimulating factor is required for bronchial eosinophilia in a murine model of allergic airway inflammation
- Creator
- Su, Yung-Chang; Rolph, Michael S.; Hansbro, Nicole G.; Mackay, Charles R.; Sewell, William A.
- Relation
- Journal of Immunology Vol. 180, Issue 4, p. 2600-2607
- Publisher Link
- http://dx.doi.org/10.4049/jimmunol.180.4.2600
- Publisher
- American Association of Immunologists
- Resource Type
- journal article
- Date
- 2008
- Description
- GM-CSF plays an important role in inflammation by promoting the production, activation, and survival of granulocytes and macrophages. In this study, GM-CSF knockout (GM-CSF⁻/⁻) mice were used to investigate the role of GM-CSF in a model of allergic airway inflammation. In allergic GM-CSF⁻/⁻ mice, eosinophil recruitment to the airways showed a striking pattern, with eosinophils present in perivascular areas, but almost completely absent in peribronchial areas, whereas in wild-type mice, eosinophil infiltration appeared in both areas. In the GM-CSF⁻/⁻ mice, mucus production in the airways was also reduced, and eosinophil numbers were markedly reduced in the bronchoalveolar lavage (BAL)³ fluid. IL-5 production was reduced in the lung tissue and BAL fluid of GM-CSF⁻/⁻ mice, but IL-4 and IL-13 production, airway hyperresponsiveness, and serum IgE levels were not affected. The presence of eosinophils in perivascular but not peribronchial regions was suggestive of a cell migration defect in the airways of GM-CSF⁻/⁻ mice. The CCR3 agonists CCL5 (RANTES) and CCL11 (eotaxin-1) were expressed at similar levels in GM-CSF⁻/⁻ and wild-type mice. However, IFN- mRNA and protein were increased in the lung tissue and BAL fluid in GM-CSF⁻/⁻ mice, as were mRNA levels of the IFN-γ-inducible chemokines CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-Tac). Interestingly, these IFN-γ-inducible chemokines are natural antagonists of CCR3, suggesting that their overproduction in GM-CSF⁻/⁻ mice contributes to the lack of airway eosinophils. These findings demonstrate distinctive abnormalities to a model of allergic asthma in the absence of GM-CSF.
- Subject
- messenger-RNA; GM-CSF; receptor expression; chemokine receptor-3; deficient mice; chronic asthma; mouse model; hyperresponsiveness; cells; CCR3
- Identifier
- http://hdl.handle.net/1959.13/43067
- Identifier
- uon:5196
- Identifier
- ISSN:0022-1767
- Language
- eng
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