Bronchial epithelial cells cultured from clinically stable lung allograft patients promote the development of macrophages from monocytes rather than dendritic cells
- C Ward1,
- K Eger1,
- J Diboll2,
- D Jones2,
- M A Haniffa2,
- M Brodlie1,
- A Fisher1,
- J L Lordan1,
- P A Corris1,
- C M U Hilkens2
- 1Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- 2The Musculoskeletal Research Groups, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- Dr C Ward, William Leech Centre, The Freeman Hospital, High Heaton, Newcastle upon Tyne NE7 7DN, UK;
- Received 3 July 2008
- Accepted 31 December 2008
- Published Online First 21 January 2009
Background: It is understood that chronic allograft failure occurs as a result of alloimmune and non-alloimmune injury. Dendritic cells (DC) are thought to be crucial in regulating (allo)immune airway damage and interactions with epithelial cells are likely. Studies in human lung transplantation are limited, however, and the available literature on DC is inconsistent. This study focused on the ex vivo influence of primary bronchial epithelial cells derived from lung allografts on DC differentiation.
Methods: Epithelial cell conditioned media (ECCM) were added to monocytes differentiating into DC under the influence of interleukin-4 and granulocyte macrophage-colony stimulating factor. The resultant cells were compared with DC cultured without ECCM and with monocyte-derived macrophages. Expression of typical DC (eg, CD1a) and macrophage (eg, CD14) markers was assessed by flow cytometry. Phenotypical assessments were complemented by functional studies of mannose receptor-mediated phagocytosis (FITC-dextran uptake) and antigen-presenting capability (mixed lymphocyte reactions).
Results: Cells exposed to ECCM expressed significantly lower levels of CD1a than unexposed DC. CD14 expression and phagocytic function were increased. ECCM cultured cells also expressed lower levels of T cell co-stimulatory molecules, secreted an anti-inflammatory cytokine profile and had significantly reduced antigen-presenting capability.
Conclusion: Using phenotypic and functional approaches, this study has shown that ECCM from lung allografts drives the production of macrophage-like cells from monocytes rather than DC. The data suggest that epithelial cells may restrain airway DC and potential alloimmunity. It is unclear whether the observed effect is specifically seen in lung transplant recipients or is a general property of bronchial epithelial cells. This may reflect a homeostatic inter-relationship between airway epithelial and DC populations relevant both to lung allografts and the lung more generally.
Additional Methods details are published online only at http://thorax.bmj.com/content/vol64/issue5
Funding: This research was funded by a Medical Research Council (MRC) project grant (to CW and PAC) and by the Arthritis Research Campaign (17750 to CMUH). MB is supported by an MRC/Cystic Fibrosis Trust Clinical Research Training Fellowship.
Competing interests: None.
Ethics approval: The study was approved by the local research ethics committee and informed consent was obtained from all participants.
CW and KE contributed equally to this work.