title: Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome.
abstract: BACKGROUND
  Mannose binding lectin (MBL) is a key mediator of both innate immunity and efferocytosis (phagocytosis of apoptotic cells) in the airway. Defective efferocytosis results in a net increase in apoptotic material that can undergo secondary necrosis, leading to tissue damage and chronic inflammation. We have shown reduced MBL and efferocytosis in other chronic inflammatory lung diseases; we therefore hypothesized that reduced MBL and efferocytosis in the airways may be a determinant of bronchiolitis obliterans syndrome (BOS) after lung transplantation.
  
  
  METHODS
  We investigated MBL (enzyme-linked immunosorbent assay [ELISA]), MBL-mediated complement deposition (UC4, ELISA), and efferocytosis of apoptotic bronchial epithelial cells (flow cytometry) in bronchoalveolar lavage (BAL) and peripheral blood from 75 lung transplant recipients, comprising 16 with stable graft function, 34 stable with proven infection, 25 with BOS, and 14 healthy controls.
  
  
  RESULTS
  In plasma, MBL levels were highly variable (0-17.538 μg/ml), but increased in infected patients vs control (p = 0.09) or stable groups (p = 0.003). There was a similar increase in UC4 in infected patients and a significant correlation between MBL and UC4. There was no correlation between MBL and time after transplant. In BAL, MBL levels were less variable (0-73.3 ng/ml) and significantly reduced in patients with BOS vs controls and stable groups. Efferocytosis was significantly reduced in the BOS group vs control and stable groups (mean [SEM] control, 20% [1.3%]; stable, 20.5% [2.5%]; infected, 17.3% [2.8%]; BOS, 11.3% [1.5%], p = 0.04).
  
  
  CONCLUSIONS
  Low levels of MBL in the airway may play a role in reduced efferocytosis, subsequent tissue damage, and BOS after lung transplantation.
authors.affiliation: Lung Research Laboratory, Hanson Institute and Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia. sandra.hodge@health.sa.gov.au
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodge
authors.forename: Melinda
authors.initials: M
authors.lastname: Dean
authors.forename: Greg
authors.initials: G
authors.lastname: Hodge
authors.forename: Mark
authors.initials: M
authors.lastname: Holmes
authors.forename: Paul N
authors.initials: PN
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001989:Bronchiolitis Obliterans / Q000150:complications / Q000378:metabolism*; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D016022:Case-Control Studies; D003181:Complement C4 / Q000378:metabolism; D057899:Cytophagocytosis / Q000502:physiology*; D006084:Graft Rejection / Q000209:etiology; D006801:Humans; D016040:Lung Transplantation; D016676:Macrophages, Alveolar / Q000473:pathology*; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D008875:Middle Aged; D011183:Postoperative Complications; D020545:Respiratory Mucosa / Q000473:pathology*; D012137:Respiratory System / Q000378:metabolism*; D013577:Syndrome
chemical_list: D003181:Complement C4; D037601:Mannose-Binding Lectin