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

Mairi Brittan1, Laura C Barr2, Niall Anderson3

  • 1BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK ; BHF Centre for Cardiovascular Science, Scottish Centre for Regenerative Medicine, The University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK.

Abstract

Insights

Novel pulmonary monocyte-like cells (PMLC) were functionally evaluated in the inflamed human lung. Inducible PMLC (iPMLC) show a pro-inflammatory, corticosteroid-resistant phenotype, distinct from resident PMLC (rPMLC).

Area of Science:

  • Immunology
  • Pulmonary Medicine
  • Cell Biology

Background:

  • Novel pulmonary monocyte-like cells (PMLC) include resident (rPMLC) and inducible (iPMLC) subpopulations.
  • iPMLC increase in bronchoalveolar lavage (BAL) fluid after lipopolysaccharide (LPS) inhalation.
  • This study provides the first functional evaluation of PMLC subpopulations in an inflamed lung model.

Purpose of the Study:

  • To functionally characterize distinct pulmonary monocyte-like cell (PMLC) subpopulations.
  • To compare the inflammatory and phagocytic capacities of resident PMLC (rPMLC) and inducible PMLC (iPMLC).
  • To assess the corticosteroid responsiveness of these cell types in acute lung inflammation.

Main Methods:

  • Quantification of iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells in BAL fluid post-LPS inhalation.
  • Flow cytometry analysis of cell surface antigens, proliferation, and phagocytosis.
  • Assessment of basal and dexamethasone-induced cytokine production by iPMLC and AM.

Main Results:

  • Resident PMLC (rPMLC) exhibit higher expression of mature macrophage markers and Ki67 compared to inducible PMLC (iPMLC).
  • Inducible PMLC (iPMLC) demonstrate a pro-inflammatory cytokine profile.
  • iPMLC display resistance to corticosteroid treatment in vitro.

Conclusions:

  • Pulmonary monocyte-like cell (PMLC) subpopulations are functionally distinct in the human lung during acute inflammation.
  • Inducible PMLC (iPMLC) contribute to inflammation and are resistant to corticosteroids.
  • These findings highlight the heterogeneity of the monocyte/macrophage lineage in lung inflammation.