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

Lookup NU author(s): Professor John SimpsonORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 (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.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.


Publication metadata

Author(s): Brittan M, Barr LC, Anderson N, Morris AC, Duffin R, Marwick JA, Rossi F, Johnson S, Dhaliwal K, Hirani N, Rossi AG, Simpson AJ

Publication type: Article

Publication status: Published

Journal: Journal of Inflammation

Year: 2014

Volume: 11

Online publication date: 31/03/2014

Acceptance date: 24/03/2014

Date deposited: 15/10/2014

ISSN (electronic): 1476-9255

Publisher: BioMed Central Ltd

URL: http://dx.doi.org/10.1186/1476-9255-11-9

DOI: 10.1186/1476-9255-11-9


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