title: Carbonic anhydrase IV is expressed on IL-5-activated murine eosinophils.
abstract: Eosinophilia and its cellular activation are hallmark features of asthma, as well as other allergic/Th2 disorders, yet there are few, if any, reliable surface markers of eosinophil activation. We have used a FACS-based genome-wide screening system to identify transcriptional alterations in murine lung eosinophils recruited and activated by pulmonary allergen exposure. Using a relatively stringent screen with false-positive correction, we identified 82 candidate genes that could serve as eosinophil activation markers and/or pathogenic effector markers in asthma. Carbonic anhydrase IV (Car4) was a top dysregulated gene with 36-fold induction in allergen-elicited pulmonary eosinophils, which was validated by quantitative PCR, immunohistochemistry, and flow cytometry. Eosinophil CAR4 expression was kinetically regulated by IL-5, but not IL-13. IL-5 was both necessary and sufficient for induction of eosinophil CAR4. Although CAR4-deficient mice did not have a defect in eosinophil recruitment to the lung, nor a change in eosinophil pH-buffering capacity, allergen-challenged chimeric mice that contained Car4(-/-) hematopoietic cells aberrantly expressed a series of genes enriched in biological processes involved in epithelial differentiation, keratinization, and anion exchange. In conclusion, we have determined that eosinophils express CAR4 following IL-5 or allergen exposure, and that CAR4 is involved in regulating the lung transcriptome associated with allergic airway inflammation; therefore, CAR4 has potential value for diagnosing and monitoring eosinophilic responses.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229; and.
authors.forename: Ting
authors.initials: T
authors.lastname: Wen
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229; and.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Mingler
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wahl
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229; and.
authors.forename: M Eyad
authors.initials: ME
authors.lastname: Khorki
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabst
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229; and.
authors.forename: Nives
authors.initials: N
authors.lastname: Zimmermann
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229; and Rothenberg@cchmc.org.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000485:Allergens / Q000235:genetics / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D030741:Carbonic Anhydrase IV / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004790:Enzyme Induction / Q000235:genetics / Q000276:immunology; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006412:Hematopoietic Stem Cells; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout
chemical_list: D000485:Allergens; D018793:Interleukin-13; D015848:Interleukin-5; D030741:Carbonic Anhydrase IV; C548248:Car4 protein, mouse