Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation
1 BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
2 Medical Research Council Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
3 Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, UK
4 Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK
5 BHF Centre for Cardiovascular Science, Scottish Centre for Regenerative Medicine, The University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK
Journal of Inflammation 2014, 11:9 doi:10.1186/1476-9255-11-9Published: 31 March 2014
We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR+CD14++CD16+cells) and inducible PMLC (iPMLC, HLA-DR+CD14++CD16- cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols.
iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed.
rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model.
These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation.