Skip to main content
Top
Published in: Journal of Inflammation 1/2014

Open Access 01-12-2014 | Research

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

Authors: Mairi Brittan, Laura C Barr, Niall Anderson, Andrew Conway Morris, Rodger Duffin, John A Marwick, Fiona Rossi, Shonna Johnson, Kev Dhaliwal, Nikhil Hirani, Adriano G Rossi, A John Simpson

Published in: Journal of Inflammation | Issue 1/2014

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Barr LC, Brittan M, Morris AC, McAuley DF, McCormack C, Fletcher AM, Richardson H, Connell M, Patel D, Wallace WA, Rossi AG, Davidson DJ, Manson L, Turner M, Hirani N, Walsh TS, Anderson NH, Dhaliwal K, Simpson AJ: An RCT of peripheral blood mononuclear cell depletion in experimental human lung inflammation. Am J Respir Crit Care Med. 2013, 188 (4): 449-55. 10.1164/rccm.201212-2334OC.PubMedCrossRef Barr LC, Brittan M, Morris AC, McAuley DF, McCormack C, Fletcher AM, Richardson H, Connell M, Patel D, Wallace WA, Rossi AG, Davidson DJ, Manson L, Turner M, Hirani N, Walsh TS, Anderson NH, Dhaliwal K, Simpson AJ: An RCT of peripheral blood mononuclear cell depletion in experimental human lung inflammation. Am J Respir Crit Care Med. 2013, 188 (4): 449-55. 10.1164/rccm.201212-2334OC.PubMedCrossRef
2.
go back to reference Brittan M, Barr L, Conway Morris A, Duffin R, Rossi F, Johnston S, Monro G, Anderson N, Rossi AG, McAuley DF, Haslett C, Hirani N, Dhaliwal K, Simpson AJ: A novel subpopulation of monocyte-like cells in the human lung after lipopolysaccharide inhalation. Eur Respir J. 2012, 40 (1): 206-214. 10.1183/09031936.00113811.PubMedCrossRef Brittan M, Barr L, Conway Morris A, Duffin R, Rossi F, Johnston S, Monro G, Anderson N, Rossi AG, McAuley DF, Haslett C, Hirani N, Dhaliwal K, Simpson AJ: A novel subpopulation of monocyte-like cells in the human lung after lipopolysaccharide inhalation. Eur Respir J. 2012, 40 (1): 206-214. 10.1183/09031936.00113811.PubMedCrossRef
3.
go back to reference Rosseau S, Hammerl P, Maus U, Walmrath HD, Schütte H, Grimminger F, Seeger W, Lohmeyer J: Phenotypic characterization of alveolar monocyte recruitment in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2000, 279 (1): L25-L35.PubMed Rosseau S, Hammerl P, Maus U, Walmrath HD, Schütte H, Grimminger F, Seeger W, Lohmeyer J: Phenotypic characterization of alveolar monocyte recruitment in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2000, 279 (1): L25-L35.PubMed
4.
go back to reference Hoogsteden HC, van Dongen JJ, van Hal PT, Delahaye M, Hop W, Hilvering C: Phenotype of blood monocytes and alveolar macrophages in interstitial lung disease. Chest. 1989, 95 (3): 574-577. 10.1378/chest.95.3.574.PubMedCrossRef Hoogsteden HC, van Dongen JJ, van Hal PT, Delahaye M, Hop W, Hilvering C: Phenotype of blood monocytes and alveolar macrophages in interstitial lung disease. Chest. 1989, 95 (3): 574-577. 10.1378/chest.95.3.574.PubMedCrossRef
5.
go back to reference Hance AJ, Douches S, Winchester RJ, Ferrans VJ, Crystal RG: Characterization of mononuclear phagocyte subpopulations in the human lung by using monoclonal antibodies: changes in alveolar macrophage phenotype associated with pulmonary sarcoidosis. J Immunol. 1985, 134 (1): 284-292.PubMed Hance AJ, Douches S, Winchester RJ, Ferrans VJ, Crystal RG: Characterization of mononuclear phagocyte subpopulations in the human lung by using monoclonal antibodies: changes in alveolar macrophage phenotype associated with pulmonary sarcoidosis. J Immunol. 1985, 134 (1): 284-292.PubMed
6.
go back to reference Barr L, Brittan M, Conway Morris A, Stewart A, Dhaliwal K, Anderson N, Turner M, Manson L, Simpson AJ: Pulmonary and systemic effects of mononuclear leukapheresis. Vox Sang. 2012, 103 (4): 275-283. 10.1111/j.1423-0410.2012.01611.x.PubMedCrossRef Barr L, Brittan M, Conway Morris A, Stewart A, Dhaliwal K, Anderson N, Turner M, Manson L, Simpson AJ: Pulmonary and systemic effects of mononuclear leukapheresis. Vox Sang. 2012, 103 (4): 275-283. 10.1111/j.1423-0410.2012.01611.x.PubMedCrossRef
7.
go back to reference Alteri E, Leonard EJ: N-formylmethionyl-leucyl-[3H]phenylalanine binding, superoxide release, and chemotactic responses of human blood monocytes that repopulate the circulation during leukapheresis. Blood. 1983, 62 (4): 918-923.PubMed Alteri E, Leonard EJ: N-formylmethionyl-leucyl-[3H]phenylalanine binding, superoxide release, and chemotactic responses of human blood monocytes that repopulate the circulation during leukapheresis. Blood. 1983, 62 (4): 918-923.PubMed
8.
go back to reference Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006, 354 (16): 1671-1684.PubMedCrossRef Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006, 354 (16): 1671-1684.PubMedCrossRef
9.
go back to reference Peter JV, John P, Graham PL, Moran JL, George IA, Bersten A: Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ. 2008, 336 (7651): 1006-1009. 10.1136/bmj.39537.939039.BE.PubMedPubMedCentralCrossRef Peter JV, John P, Graham PL, Moran JL, George IA, Bersten A: Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ. 2008, 336 (7651): 1006-1009. 10.1136/bmj.39537.939039.BE.PubMedPubMedCentralCrossRef
10.
go back to reference Meduri GU, Golden E, Freire AX, Taylor E, Zaman M, Carson SJ, Gibson M, Umberger R: Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest. 2007, 131 (4): 954-963. 10.1378/chest.06-2100.PubMedCrossRef Meduri GU, Golden E, Freire AX, Taylor E, Zaman M, Carson SJ, Gibson M, Umberger R: Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest. 2007, 131 (4): 954-963. 10.1378/chest.06-2100.PubMedCrossRef
11.
go back to reference Marik PE, Meduri GU, Rocco PR, Annane D: Glucocorticoid treatment in acute lung injury and acute respiratory distress syndrome. Crit Care Clin. 2011, 27 (3): 589-607. 10.1016/j.ccc.2011.05.007.PubMedCrossRef Marik PE, Meduri GU, Rocco PR, Annane D: Glucocorticoid treatment in acute lung injury and acute respiratory distress syndrome. Crit Care Clin. 2011, 27 (3): 589-607. 10.1016/j.ccc.2011.05.007.PubMedCrossRef
12.
go back to reference Ward C, Hannah S, Chilvers ER, Farrow S, Haslett C, Rossi AG: Transforming growth factor-beta increases the inhibitory effects of GM-CSF and dexamethasone on neutrophil apoptosis. Biochem Soc Trans. 1997, 25 (2): 244S-PubMedCrossRef Ward C, Hannah S, Chilvers ER, Farrow S, Haslett C, Rossi AG: Transforming growth factor-beta increases the inhibitory effects of GM-CSF and dexamethasone on neutrophil apoptosis. Biochem Soc Trans. 1997, 25 (2): 244S-PubMedCrossRef
Metadata
Title
Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation
Authors
Mairi Brittan
Laura C Barr
Niall Anderson
Andrew Conway Morris
Rodger Duffin
John A Marwick
Fiona Rossi
Shonna Johnson
Kev Dhaliwal
Nikhil Hirani
Adriano G Rossi
A John Simpson
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2014
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/1476-9255-11-9

Other articles of this Issue 1/2014

Journal of Inflammation 1/2014 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.