title: Gq signaling is required for allergen-induced pulmonary eosinophilia.
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.
authors.affiliation: Division of Pulmonary Medicine, Mayo Clinic, Scottsdale AZ 85259, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Borchers
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Justice
authors.forename: Tracy
authors.initials: T
authors.lastname: Ansay
authors.forename: Valeria
authors.initials: V
authors.lastname: Mancino
authors.forename: Michael P
authors.initials: MP
authors.lastname: McGarry
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crosby
authors.forename: Melvin I
authors.initials: MI
authors.lastname: Simon
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000336:Aerosols; D000485:Allergens; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins