Abstract
The complexity and magnitude of interactions leading to the selective infiltration of eosinophils in response to inhaled allergens are formidable obstacles to a larger understanding of the pulmonary pathology associated with allergic asthma. This study uses knockout mice to demonstrate a novel function for the heterotrimeric G protein, G(q), in the regulation of pulmonary eosinophil recruitment. In the absence of G(q) signaling, eosinophils failed to accumulate in the lungs following allergen challenge. These studies demonstrate that the inhibition of eosinophil accumulation in the airways is attributed to the failure of hemopoietically derived cells to elaborate GM-CSF in the airways. The data suggest that activation of a G(q)-coupled receptor(s) on resident leukocytes in the lung elicits expression of GM-CSF, which, in turn, is required for allergen-induced pulmonary eosinophilia, identifying a novel pathway of eosinophil-associated effector functions leading to pulmonary pathology in diseases such as asthma.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aerosols
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Allergens / administration & dosage*
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Animals
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology
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Chemotactic Factors, Eosinophil / pharmacology
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Chemotaxis, Leukocyte / genetics
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Chemotaxis, Leukocyte / immunology
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Cytokines / biosynthesis
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Female
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GTP-Binding Protein alpha Subunits, Gq-G11
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Heterotrimeric GTP-Binding Proteins / deficiency
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Heterotrimeric GTP-Binding Proteins / genetics
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Heterotrimeric GTP-Binding Proteins / physiology*
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Injections, Intraperitoneal
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Intubation, Intratracheal
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Leukocyte Count
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Lymphocyte Activation / genetics
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Mice
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Mice, Knockout
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Mice, Transgenic
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Ovalbumin / administration & dosage
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Ovalbumin / immunology
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Pulmonary Eosinophilia / etiology
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Pulmonary Eosinophilia / genetics
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Pulmonary Eosinophilia / immunology*
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Pulmonary Eosinophilia / pathology
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Signal Transduction / immunology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Aerosols
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Allergens
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Chemotactic Factors, Eosinophil
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Cytokines
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Granulocyte-Macrophage Colony-Stimulating Factor
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Ovalbumin
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GTP-Binding Protein alpha Subunits, Gq-G11
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Heterotrimeric GTP-Binding Proteins