title: A novel subpopulation of monocyte-like cells in the human lung after lipopolysaccharide inhalation.
abstract: The co-ordinated recruitment of monocyte subpopulations, neutrophils and regulatory T-cells (Tregs) during the early stages of human acute lung inflammation remains poorly understood. We therefore performed a detailed characterisation of these lineages in the blood and lungs in a model of human acute lung inflammation. Healthy volunteers inhaled lipopolysaccharide (LPS) or saline (n=6 for each group). Blood was collected at 0, 2, 4, 6 and 8 h and bronchoscopy with bronchoalveolar lavage (BAL) performed at 8 h. Multiparameter flow cytometry was used to characterise monocyte subpopulations, neutrophils and Tregs in the blood and lung. Inhalation of LPS was associated with significant blood and BAL fluid neutrophilia. Blood populations of monocyte subpopulations and Tregs were unaltered by LPS. In contrast, LPS induced an accumulation of a pulmonary monocyte-like cell (PMLC) population, which was further subdivided into "inducible" CD14(++)CD16(-) and "resident" CD14(++)CD16(+) subsets. Inducible PMLCs were significantly increased following LPS inhalation (p=0.0046), whereas resident PMLCs were unchanged. In addition, we noted a significant decrease in Tregs in BAL fluid with LPS inhalation (p=0.027). The early stages of LPS-induced inflammation in humans is characterised by pulmonary accumulation of a novel inducible monocyte-like subpopulation, accompanied by significant changes in both neutrophil and Treg numbers.
authors.affiliation: University of Edinburgh MRC Centre for Inflammation Research, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. mbrittan@staffmail.ed.ac.uk
authors.forename: Mairi
authors.initials: M
authors.lastname: Brittan
authors.forename: Laura
authors.initials: L
authors.lastname: Barr
authors.forename: Andrew
authors.initials: A
authors.lastname: Conway Morris
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.forename: Fiona
authors.initials: F
authors.lastname: Rossi
authors.forename: Shonna
authors.initials: S
authors.lastname: Johnston
authors.forename: Graham
authors.initials: G
authors.lastname: Monro
authors.forename: Niall
authors.initials: N
authors.lastname: Anderson
authors.forename: Adriano G
authors.initials: AG
authors.lastname: Rossi
authors.forename: Danny F
authors.initials: DF
authors.lastname: McAuley
authors.forename: Christopher
authors.initials: C
authors.lastname: Haslett
authors.forename: Nik
authors.initials: N
authors.lastname: Hirani
authors.forename: Kev
authors.initials: K
authors.lastname: Dhaliwal
authors.forename: A John
authors.initials: AJ
authors.lastname: Simpson
mesh_terms: D000293:Adolescent; D000328:Adult; D018893:Bronchoalveolar Lavage; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D001239:Inhalation; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008168:Lung / Q000276:immunology*; D008297:Male; D009000:Monocytes; D011014:Pneumonia / Q000276:immunology*; D013601:T-Lymphocytes; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides