Publication:

Azithromycin attenuates effects of lipopolysaccharide on lung allograft bronchial epithelial cells (2008)

Author(s): Murphy DM, Forrest IA, Corris PA, Johnson GE, Small T, Jones D, Fisher AJ, Egan JJ, Cawston TE, Lordan JL, Ward C

    Abstract: BackgroundThe bronchial epithelium is a source of mediators that may play a role in the airway inflammation and remodeling of post-transplant obliterative bronchiolitis (OB). Traditional strategies have failed to have an impact on OB. Recent studies have suggested a role for azithromycin in managing the condition. In this study we aimed to determine the effect of azithromycin on LPS-mediated epithelial release of factors relevant to airway neutrophilia and remodeling in a unique population of primary bronchial epithelial cells (PBECs) derived from stable lung allografts. MethodsPBECs were established from bronchial brushings of stable lung transplant recipients and treated with lipopolysaccharide (LPS, 0.1, 1 and 10 μg/ml) for 48 hours. Interleukin-8 (IL-8), granulocyte macrophage colony-stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF) protein levels were measured by Luminex analyzer. PBECs were then incubated with LPS and azithromycin, and protein levels were again determined. ResultsLPS caused a significant increase in IL-8 and GM-CSF at concentrations of 1 and 10 μg/ml, with no effect on VEGF release. Azithromycin caused a significant decrease in the LPS-stimulated IL-8 and GM-CSF release. ConclusionsLPS upregulates release of IL-8 and GM-CSF from PBECs derived from stable lung allografts. Sub-microbicidal concentrations of azithromycin attenuate this and may, therefore, alleviate infection-driven neutrophilic airway inflammation and remodeling in the allograft airway.

      • Date: 01-10-2008
      • Journal: The Journal of Heart and Lung Transplantation
      • Volume: 27
      • Issue: 11
      • Pages: 1210-6
      • Publisher: Elsevier Inc.
      • Publication type: Article
      • Bibliographic status: Published
      Staff

      Professor Tim Cawston
      Strategic Res Advisor (William Leech) and William Leech Professor of Rheumatology

      • Telephone: +44 (0) 191 208 5363

      Professor Andrew Fisher
      Associate Dean for Clinical Academic Training and Professor of Respiratory Transplant Medicine

      Dr Ian Forrest
      Honorary Clinical Senior Lecturer

      Dr Christopher Ward
      Senior Lecturer; Respiratory Medicine