title: Chronic β-adrenoceptor antagonists upregulate the rat alveolar macrophage adrenergic system through the β1-subtype.
abstract: BACKGROUND
  Previous studies demonstrate that macrophages synthesis and release catecholamines, which regulate the immune responses in an autocrine manner. These responses are mediated in part by β-adrenoceptors expressed on macrophages. Some β-adrenoceptor antagonists are commonly used in clinical conditions. Here we investigated whether the chronic administration of β-adrenoceptor antagonists upregulate adrenergic system of alveolar macrophage and the potential mechanims.
  
  
  METHODS
  Propranolol (30 mg/kg·d) or atenolol (5 mg/kg·d) was administered by gavage to rats for 4 weeks. Then alveolar macrophages were isolated and the expression of β(1) or β(2)-adrenoceptor was detected by flow cytometric analysis. Dopamine β-hydroxylase expression was assessed by Western blot assay and the concentrations of noradrenaline, IL-6, and TNF-α in cell supernatants were measured using ELISA after 2 h or 24 h exposure of alveolar macrophages to 100 ng/ml lipopolysaccharide (LPS).
  
  
  RESULTS
  Propranolol increased the mean fluorescence intensity (MFI) of β(1), β(2)-adrenoceptor and the frequency of β(1)-,β(2)- adrenoceptor positive macrophages. However, only the MFI of β(1)-adrenoceptor and the frequency of β(1)-adrenoceptor positive macrophages were increased by atenolol. Furthermore, both propranolol and atenolol promoted LPS-mediated dopamine β-hydroxylase protein expression and increased noradrenaline production in rat alveolar macrophages. This was accompanied by increased LPS-mediated IL-6 and TNF-α production in cell supernatants of alveolar macrophages.
  
  
  CONCLUSIONS
  These findings demonstrate that propranolol or atenolol upregulates alveolar macrophage adrenergic system, and the response may be β(1)-adrenergic receptor subtype dependent.
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Qi
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Cui
authors.forename: Zi-Yong
authors.initials: ZY
authors.lastname: Yue
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Li
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D005456:Fluorescent Dyes; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; D001262:Atenolol; D011433:Propranolol; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine