Gq signaling is required for allergen-induced pulmonary eosinophilia.
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.
Borchers
Michael T
MT
Division of Pulmonary Medicine, Mayo Clinic, Scottsdale AZ 85259, USA.
Justice
Paul J
PJ
Ansay
Tracy
T
Mancino
Valeria
V
McGarry
Michael P
MP
Crosby
Jeffrey
J
Simon
Melvin I
MI
Lee
Nancy A
NA
Lee
James J
JJ
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
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