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Open Access Research

Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation

Mairi Brittan15*, Laura C Barr2, Niall Anderson3, Andrew Conway Morris2, Rodger Duffin2, John A Marwick2, Fiona Rossi2, Shonna Johnson2, Kev Dhaliwal2, Nikhil Hirani2, Adriano G Rossi2 and A John Simpson24

Author Affiliations

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

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Journal of Inflammation 2014, 11:9  doi:10.1186/1476-9255-11-9

Published: 31 March 2014

Abstract

Background

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.

Methods

iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (nā€‰=ā€‰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.

Results

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.

Conclusions

These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation.

Keywords:
Monocytes; Macrophages; Acute lung inflammation; Lipopolysaccharide; Multiparameter flow cytometry; Corticosteroid