title: Impact of adiponectin deficiency on pulmonary responses to acute ozone exposure in mice.
abstract: Obese mice have increased responses to acute ozone (O(3)) exposure. T-cadherin is a binding protein for the high-molecular weight isoforms of adiponectin, an anti-inflammatory hormone that declines in obesity. The objective of the present study was to determine whether adiponectin affects pulmonary responses to O(3), and whether these effects are mediated through T-cadherin. We performed bronchoalveolar lavage (BAL) and measured pulmonary responsiveness to methacholine after acute air or O(3) exposure (2 ppm for 3 h) in adiponectin-deficient (Adipo(-/-)) or T-cadherin-deficient (T-Cad(-/-)) mice. O(3) increased pulmonary responses to methacholine and increased BAL neutrophils and protein to a greater extent in wild-type than in Adipo(-/-) mice, whereas T-cadherin deficiency had no effect. O(3)-induced increases in BAL IL-6 and keratinocyte-derived chemokine (KC), which contribute to O(3)-induced pulmonary neutrophilia, were also greater in wild-type than in Adipo(-/-) mice. In contrast, responses to O(3) were not altered by transgenic overexpression of adiponectin. To determine which adiponectin isoforms are present in the lung, Western blotting was performed. The hexameric isoform of adiponectin dominated in serum, whereas BAL was dominated by the high-molecular weight isoform of adiponectin. Interestingly, serum adiponectin was greater in T-Cad(-/-) versus wild-type mice, whereas BAL adiponectin was lower in T-Cad(-/-) versus wild-type mice, suggesting that T-cadherin may be important for transit of high-molecular weight adiponectin from the blood to the lung. Our results indicate that adiponectin deficiency inhibits pulmonary inflammation induced by acute O(3) exposure, and that T-cadherin does not mediate the effects of adiponectin responsible for these events.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Christopher
authors.initials: C
authors.lastname: Hug
authors.forename: David I
authors.initials: DI
authors.lastname: Kasahara
authors.forename: Richard A
authors.initials: RA
authors.lastname: Johnston
authors.forename: Alison S
authors.initials: AS
authors.lastname: Williams
authors.forename: Norah G
authors.initials: NG
authors.lastname: Verbout
authors.forename: Huiqing
authors.initials: H
authors.lastname: Si
authors.forename: Jordan
authors.initials: J
authors.lastname: Jastrab
authors.forename: Amit
authors.initials: A
authors.lastname: Srivastava
authors.forename: Erin S
authors.initials: ES
authors.lastname: Williams
authors.forename: Barbara
authors.initials: B
authors.lastname: Ranscht
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Shore
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000172:deficiency* / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015820:Cadherins / Q000172:deficiency / Q000378:metabolism; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000008:administration & dosage* / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D052242:Adiponectin; D015820:Cadherins; D016207:Cytokines; D020033:Protein Isoforms; D010126:Ozone