title: Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice.
abstract: Adiponectin is an adipocyte-derived collectin that acts on a wide range of tissues including liver, brain, heart, and vascular endothelium. To date, little is known about the actions of adiponectin in the lung. Herein, we demonstrate that adiponectin is present in lung lining fluid and that adiponectin deficiency leads to increases in proinflammatory mediators and an emphysema-like phenotype in the mouse lung. Alveolar macrophages from adiponectin-deficient mice spontaneously display increased production of tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase (MMP-12) activity. Consistent with these observations, we found that pretreatment of alveolar macrophages with adiponectin leads to TNF-alpha and MMP-12 suppression. Together, our findings show that adiponectin leads to macrophage suppression in the lung and suggest that adiponectin-deficient states may contribute to the pathogenesis of inflammatory lung conditions such as emphysema.
authors.affiliation: The Pulmonary Center, R-304, Boston Univ. School of Medicine, 80 E. Concord St., Boston, MA 02118, USA. rsummer@bu.edu
authors.forename: R
authors.initials: R
authors.lastname: Summer
authors.forename: F F
authors.initials: FF
authors.lastname: Little
authors.forename: N
authors.initials: N
authors.lastname: Ouchi
authors.forename: Y
authors.initials: Y
authors.lastname: Takemura
authors.forename: T
authors.initials: T
authors.lastname: Aprahamian
authors.forename: D
authors.initials: D
authors.lastname: Dwyer
authors.forename: K
authors.initials: K
authors.lastname: Fitzsimmons
authors.forename: B
authors.initials: B
authors.lastname: Suki
authors.forename: H
authors.initials: H
authors.lastname: Parameswaran
authors.forename: A
authors.initials: A
authors.lastname: Fine
authors.forename: K
authors.initials: K
authors.lastname: Walsh
mesh_terms: D052242:Adiponectin / Q000172:deficiency*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004646:Emphysema / Q000209:etiology / Q000503:physiopathology*; D008168:Lung / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D052242:Adiponectin; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases