title: Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice.
abstract: Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpe(fat) mice). Accordingly, Cpe(fat) and lean, wild-type (C57BL/6) mice were sensitized to OVA and then challenged with either aerosolized PBS or OVA. Compared with genotype-matched, OVA-sensitized and PBS-challenged mice, OVA sensitization and challenge elicited airway obstruction and increased BALF eosinophils, macrophages, neutrophils, IL-4, IL-13, IL-18, and chemerin. However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpe(fat) compared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model.
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Paul H
authors.initials: PH
authors.lastname: Dahm
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts;
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Richards
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Harry
authors.initials: H
authors.lastname: Karmouty-Quintana
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York;
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Cromar
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston School of Medicine, Galveston, Texas;
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Sur
authors.affiliation: Comparative Pathology Laboratory, Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas;
authors.forename: Roger E
authors.initials: RE
authors.lastname: Price
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Farhan
authors.initials: F
authors.lastname: Malik
authors.affiliation: Pediatric Pulmonary Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas; and.
authors.forename: Chantal Y
authors.initials: CY
authors.lastname: Spencer
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Ramon X
authors.initials: RX
authors.lastname: Barreno
authors.affiliation: Pediatric Research Center, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas.
authors.forename: Syed S
authors.initials: SS
authors.lastname: Hashmi
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Michael R
authors.initials: MR
authors.lastname: Blackburn
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Ikram U
authors.initials: IU
authors.lastname: Haque
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas; Pediatric Research Center, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas Richard.A.Johnston@uth.tmc.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Johnston
mesh_terms: D000402:Airway Obstruction / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D000403:Airway Resistance; D000818:Animals; D000941:Antigens; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D043423:Carboxypeptidase H / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D007136:Immunoglobulins / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D010047:Ovalbumin; D010641:Phenotype; D011014:Pneumonia / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000941:Antigens; D015415:Biomarkers; D007136:Immunoglobulins; D018836:Inflammation Mediators; D010047:Ovalbumin; D043423:Carboxypeptidase H
keywords: asthma; atopic; eosinophil; interleukin-13; ovalbumin