title: Adiponectin deficiency increases allergic airway inflammation and pulmonary vascular remodeling.
abstract: Obesity is associated with an increased incidence and severity of asthma, as well as other lung disorders, such as pulmonary hypertension. Adiponectin (APN), an antiinflammatory adipocytokine, circulates at lower levels in the obese, which is thought to contribute to obesity-related inflammatory diseases. We sought to determine the effects of APN deficiency in a murine model of chronic asthma. Allergic airway inflammation was induced in APN-deficient mice (APN(-/-)) using sensitization without adjuvant followed by airway challenge with ovalbumin. The mice were then analyzed for changes in inflammation and lung remodeling. APN(-/-) mice in this model develop increased allergic airway inflammation compared with wild-type mice, with greater accumulation of eosinophils and monocytes in the airways associated with elevated lung chemokine levels. Surprisingly, APN(-/-) mice developed severe pulmonary arterial muscularization and pulmonary arterial hypertension in this model, whereas wild-type mice had only mild vascular remodeling and comparatively less pulmonary arterial hypertension. Our findings demonstrate that APN modulates allergic inflammation and pulmonary vascular remodeling in a model of chronic asthma. These data provide a possible mechanism for the association between obesity and asthma, and suggest a potential novel link between obesity, inflammatory lung disease, and pulmonary hypertension.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, CNY 8301, 149 13th Street, Charlestown, MA 02129, USA. bmedoff@partners.org
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Patricio
authors.initials: P
authors.lastname: Leyton
authors.forename: Meiqian
authors.initials: M
authors.lastname: Weng
authors.forename: Barry P
authors.initials: BP
authors.lastname: Sandall
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Raher
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D052242:Adiponectin / Q000172:deficiency; D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D006965:Hyperplasia; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D008170:Lung Compliance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D011651:Pulmonary Artery / Q000473:pathology; D011657:Pulmonary Eosinophilia / Q000209:etiology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D018925:Chemokines; D010047:Ovalbumin