Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Respiratory Research
Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

Human lung and monocyte-derived macrophages differ with regard to the effects of β2-adrenoceptor agonists on cytokine release

Authors: Tatiana Victoni, Hélène Salvator, Charlotte Abrial, Marion Brollo, Luis Cristovão Sobrino Porto, Vincent Lagente, Emmanuel Naline, Stanislas Grassin-Delyle, Philippe Devillier

Published in: Respiratory Research | Issue 1/2017

Login to get access

Abstract

Background

β2-adrenoceptor agonists have been shown to reduce the lipopolysaccharide (LPS)-induced cytokine release by human monocyte-derived macrophages (MDMs). We compare the expression of β2-adrenoceptors and the inhibitory effect of formoterol and salmeterol on the LPS-induced release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and a range of chemokines (CCL2, 3, 4, and IL-8) by human lung macrophages (LMs) and MDMs.

Methods

LMs were isolated from patients undergoing resection and MDMs were obtained from blood monocytes in the presence of GM-CSF. LMs and MDMs were incubated in the absence or presence of formoterol or salmeterol prior to stimulation with LPS. The effects of formoterol were also assessed in the presence of the phosphodiesterase inhibitor roflumilast.

Results

LPS-induced cytokine production was higher in LMs than in MDMs. Salmeterol and formoterol exerted an inhibitory effect on the LPS-induced production of TNF-α, IL-6, CCL2, CCL3, and CCL4 in MDMs. In contrast, the β2-adrenoceptor agonists were devoid of any effect on LMs - even in the presence of roflumilast. The expression of β2-adrenergic receptors was detected on Western blots in MDMs but not in LMs.

Conclusions

Concentrations of β2-adrenoceptor agonists that cause relaxation of the human bronchus can inhibit cytokine production by LPS-stimulated MDMs but not by LMs.
Appendix
Available only for authorised users
Literature
1.
Nelson Jr RP, DiNicolo R, Fernandez-Caldas E, Seleznick MJ, Lockey RF, Good RA. Allergen-specific IgE levels and mite allergen exposure in children with acute asthma first seen in an emergency department and in nonasthmatic control subjects. J Allergy Clin Immunol. 1996;98:258–63.CrossRefPubMed
2.
Salo PM, Calatroni A, Gergen PJ, Hoppin JA, Sever ML, Jaramillo R, Arbes Jr SJ, Zeldin DC. Allergy-related outcomes in relation to serum IgE: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy Clin Immunol. 2011;127:1226–35. e1227.CrossRefPubMedPubMedCentral
3.
Terreehorst I, Oosting AJ, Tempels-Pavlica Z, de Monchy JG, Bruijnzeel-Koomen CA, Hak E, van Wijk RG. Prevalence and severity of allergic rhinitis in house dust mite-allergic patients with bronchial asthma or atopic dermatitis. Clin Exp Allergy. 2002;32:1160–5.CrossRefPubMed
4.
To T, Feldman L, Simatovic J, Gershon AS, Dell S, Su J, Foty R, Licskai C. Health risk of air pollution on people living with major chronic diseases: a Canadian population-based study. BMJ Open. 2015;5:e009075.CrossRefPubMedPubMedCentral
5.
To T, Zhu J, Larsen K, Simatovic J, Feldman L, Ryckman K, Gershon A, Lougheed MD, Licskai C, Chen H, et al. Progression from asthma to chronic obstructive pulmonary disease. Is air pollution a risk factor? Am J Respir Crit Care Med. 2016;194:429–38.CrossRefPubMed
6.
Bauer RN, Diaz-Sanchez D, Jaspers I. Effects of air pollutants on innate immunity: the role of Toll-like receptors and nucleotide-binding oligomerization domain-like receptors. J Allergy Clin Immunol. 2012;129:14–24. quiz 25–16.CrossRefPubMedPubMedCentral
7.
8.
Lam D, Ng N, Lee S, Batzer G, Horner AA. Airway house dust extract exposures modify allergen-induced airway hypersensitivity responses by TLR4-dependent and independent pathways. J Immunol. 2008;181:2925–32.CrossRefPubMedPubMedCentral
9.
Minnicozzi M, Sawyer RT, Fenton MJ. Innate immunity in allergic disease. Immunol Rev. 2011;242:106–27.CrossRefPubMed
10.
11.
Hosoki K, Itazawa T, Boldogh I, Sur S. Neutrophil recruitment by allergens contribute to allergic sensitization and allergic inflammation. Curr Opin Allergy Clin Immunol. 2016;16:45–50.CrossRefPubMedPubMedCentral
12.
Bosmann M, Grailer JJ, Zhu K, Matthay MA, Sarma JV, Zetoune FS, Ward PA. Anti-inflammatory effects of beta2 adrenergic receptor agonists in experimental acute lung injury. FASEB J. 2012;26:2137–44.CrossRefPubMedPubMedCentral
13.
Maris NA, van der Sluijs KF, Florquin S, de Vos AF, Pater JM, Jansen HM, van der Poll T. Salmeterol, a beta2-receptor agonist, attenuates lipopolysaccharide-induced lung inflammation in mice. Am J Physiol Lung Cell Mol Physiol. 2004;286:L1122–8.CrossRefPubMed
14.
Wex E, Kollak I, Duechs MJ, Naline E, Wollin L, Devillier P. The long-acting beta2 -adrenoceptor agonist olodaterol attenuates pulmonary inflammation. Br J Pharmacol. 2015;172:3537–47.CrossRefPubMedPubMedCentral
15.
Maris NA, de Vos AF, Dessing MC, Spek CA, Lutter R, Jansen HM, van der Zee JS, Bresser P, van der Poll T. Antiinflammatory effects of salmeterol after inhalation of lipopolysaccharide by healthy volunteers. Am J Respir Crit Care Med. 2005;172:878–84.CrossRefPubMed
16.
Ikeda T, Anisuzzaman AS, Yoshiki H, Sasaki M, Koshiji T, Uwada J, Nishimune A, Itoh H, Muramatsu I. Regional quantification of muscarinic acetylcholine receptors and beta-adrenoceptors in human airways. Br J Pharmacol. 2012;166:1804–14.CrossRefPubMedPubMedCentral
17.
Spina D, Rigby PJ, Paterson JW, Goldie RG. Autoradiographic localization of beta-adrenoceptors in asthmatic human lung. Am Rev Respir Dis. 1989;140:1410–5.CrossRefPubMed
18.
Barnes PJ, Basbaum CB, Nadel JA, Roberts JM. Localization of beta-adrenoreceptors in mammalian lung by light microscopic autoradiography. Nature. 1982;299:444–7.CrossRefPubMed
19.
Carstairs JR, Nimmo AJ, Barnes PJ. Autoradiographic visualization of beta-adrenoceptor subtypes in human lung. Am Rev Respir Dis. 1985;132:541–7.PubMed
20.
Barnes PJ. Effect of beta-agonists on inflammatory cells. J Allergy Clin Immunol. 1999;104:S10–7.CrossRefPubMed
21.
Hjemdahl P, Larsson K, Johansson MC, Zetterlund A, Eklund A. Beta-adrenoceptors in human alveolar macrophages isolated by elutriation. Br J Clin Pharmacol. 1990;30:673–82.CrossRefPubMedPubMedCentral
22.
Liggett SB. Identification and characterization of a homogeneous population of beta 2-adrenergic receptors on human alveolar macrophages. Am Rev Respir Dis. 1989;139:552–5.CrossRefPubMed
23.
Anderson R, Theron AJ, Steel HC, Durandt C, Tintinger GR, Feldman C. The beta-2-adrenoreceptor agonists, formoterol and indacaterol, but not salbutamol, effectively suppress the reactivity of human neutrophils in vitro. Mediators Inflamm. 2014;2014:105420.CrossRefPubMedPubMedCentral
24.
Ezeamuzie CI, Shihab PK, Al-Radwan R. Loss of surface beta-2 adrenoceptors accounts for the insensitivity of cultured human monocytes to beta-2 adrenoceptor agonists. Int Immunopharmacol. 2011;11:1189–94.CrossRefPubMed
25.
Li CY, Tsai CS, Chueh SH, Hsu PC, Wang JY, Wong CS, Ho ST. Dobutamine inhibits monocyte chemoattractant protein-1 production and chemotaxis in human monocytes. Anesth Analg. 2003;97:205–9. table of contents.CrossRefPubMed
26.
Li CY, Tsai CS, Hsu PC, Wu CT, Wong CS, Ho ST. Dobutamine modulates lipopolysaccharide-induced macrophage inflammatory protein-1alpha and interleukin-8 production in human monocytes. Anesth Analg. 2003;97:210–5. table of contents.CrossRefPubMed
27.
Linden M. The effects of beta 2-adrenoceptor agonists and a corticosteroid, budesonide, on the secretion of inflammatory mediators from monocytes. Br J Pharmacol. 1992;107:156–60.CrossRefPubMedPubMedCentral
28.
Yoshimura T, Kurita C, Nagao T, Usami E, Nakao T, Watanabe S, Kobayashi J, Yamazaki F, Tanaka H, Inagaki N, Nagai H. Inhibition of tumor necrosis factor-alpha and interleukin-1-beta production by beta-adrenoceptor agonists from lipopolysaccharide-stimulated human peripheral blood mononuclear cells. Pharmacology. 1997;54:144–52.CrossRefPubMed
29.
Yoshimura T, Kurita C, Nagao T, Usami E, Nakao T, Watanabe S, Kobayashi J, Yamazaki F, Tanaka H, Nagai H. Effects of cAMP-phosphodiesterase isozyme inhibitor on cytokine production by lipopolysaccharide-stimulated human peripheral blood mononuclear cells. Gen Pharmacol. 1997;29:633–8.CrossRefPubMed
30.
Donnelly LE, Tudhope SJ, Fenwick PS, Barnes PJ. Effects of formoterol and salmeterol on cytokine release from monocyte-derived macrophages. Eur Respir J. 2010;36:178–86.CrossRefPubMed
31.
Izeboud CA, Monshouwer M, van Miert AS, Witkamp RF. The beta-adrenoceptor agonist clenbuterol is a potent inhibitor of the LPS-induced production of TNF-alpha and IL-6 in vitro and in vivo. Inflamm Res. 1999;48:497–502.CrossRefPubMed
32.
Sarir H, Mortaz E, Karimi K, Johnson M, Nijkamp FP, Folkerts G. Combination of fluticasone propionate and salmeterol potentiates the suppression of cigarette smoke-induced IL-8 production by macrophages. Eur J Pharmacol. 2007;571:55–61.CrossRefPubMed
33.
Jin M, Opalek JM, Marsh CB, Wu HM. Proteome comparison of alveolar macrophages with monocytes reveals distinct protein characteristics. Am J Respir Cell Mol Biol. 2004;31:322–9.CrossRefPubMed
34.
Tomechko SE, Lundberg KC, Jarvela J, Bebek G, Chesnokov NG, Schlatzer D, Ewing RM, Boom WH, Chance MR, Silver RF. Proteomic and bioinformatics profile of paired human alveolar macrophages and peripheral blood monocytes. Proteomics. 2015;15:3797–805.CrossRefPubMed
35.
Groot-Kormelink PJ, Fawcett L, Wright PD, Gosling M, Kent TC. Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates. BMC Immunol. 2012;13:57.CrossRefPubMedPubMedCentral
36.
Li J, Pritchard DK, Wang X, Park DR, Bumgarner RE, Schwartz SM, Liles WC. cDNA microarray analysis reveals fundamental differences in the expression profiles of primary human monocytes, monocyte-derived macrophages, and alveolar macrophages. J Leukoc Biol. 2007;81:328–35.CrossRefPubMed
37.
Fuller RW, O’Malley G, Baker AJ, MacDermot J. Human alveolar macrophage activation: inhibition by forskolin but not beta-adrenoceptor stimulation or phosphodiesterase inhibition. Pulm Pharmacol. 1988;1:101–6.CrossRefPubMed
38.
Baker AJ, Palmer J, Johnson M, Fuller RW. Inhibitory actions of salmeterol on human airway macrophages and blood monocytes. Eur J Pharmacol. 1994;264:301–6.CrossRefPubMed
39.
Zetterlund A, Linden M, Larsson K. Effects of beta2-agonists and budesonide on interleukin-1beta and leukotriene B4 secretion: studies of human monocytes and alveolar macrophages. J Asthma. 1998;35:565–73.CrossRefPubMed
40.
Zetterlund A, Hjemdahl P, Larsson K. beta2-Adrenoceptor desensitization in human alveolar macrophages induced by inhaled terbutaline in vivo is not counteracted by budesonide. Clin Sci (Lond). 2001;100:451–7.CrossRef
41.
Gill SK, Yao Y, Kay LJ, Bewley MA, Marriott HM, Peachell PT. The anti-inflammatory effects of PGE2 on human lung macrophages are mediated by the EP4 receptor. Br J Pharmacol. 2016;173:3099–109.CrossRefPubMed
42.
Birrell MA, Maher SA, Dekkak B, Jones V, Wong S, Brook P, Belvisi MG. Anti-inflammatory effects of PGE2 in the lung: role of the EP4 receptor subtype. Thorax. 2015;70:740–7.CrossRefPubMedPubMedCentral
43.
Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P. The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010;159:1304–11.CrossRefPubMedPubMedCentral
44.
Buenestado A, Grassin-Delyle S, Guitard F, Naline E, Faisy C, Israel-Biet D, Sage E, Bellamy JF, Tenor H, Devillier P. Roflumilast inhibits the release of chemokines and TNF-alpha from human lung macrophages stimulated with lipopolysaccharide. Br J Pharmacol. 2012;165:1877–90.CrossRefPubMedPubMedCentral
45.
Gill SK, Marriott HM, Suvarna SK, Peachell PT. Evaluation of the anti-inflammatory effects of beta-adrenoceptor agonists on human lung macrophages. Eur J Pharmacol. 2016;793:49–55.
46.
Bouyssou T, Casarosa P, Naline E, Pestel S, Konetzki I, Devillier P, Schnapp A. Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models. J Pharmacol Exp Ther. 2010;334:53–62.CrossRefPubMed
47.
Naline E, Trifilieff A, Fairhurst RA, Advenier C, Molimard M. Effect of indacaterol, a novel long-acting beta2-agonist, on isolated human bronchi. Eur Respir J. 2007;29:575–81.CrossRefPubMed
48.
Gicquel T, Victoni T, Fautrel A, Robert S, Gleonnec F, Guezingar M, Couillin I, Catros V, Boichot E, Lagente V. Involvement of purinergic receptors and NOD-like receptor-family protein 3-inflammasome pathway in the adenosine triphosphate-induced cytokine release from macrophages. Clin Exp Pharmacol Physiol. 2014;41:279–86.CrossRefPubMed
49.
Hatzelmann A, Schudt C. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. J Pharmacol Exp Ther. 2001;297:267–79.PubMed
50.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25:402–8.CrossRefPubMed
51.
Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, Horuk R, Sparre-Ulrich AH, Locati M, Luster AD, et al. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev. 2014;66:1–79.CrossRefPubMedPubMedCentral
52.
Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet. 2011;378:1015–26.CrossRefPubMed
53.
Ravi AK, Khurana S, Lemon J, Plumb J, Booth G, Healy L, Catley M, Vestbo J, Singh D. Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum. Respir Res. 2014;15:103.CrossRefPubMedPubMedCentral
54.
Tsukamoto H, Fukudome K, Takao S, Tsuneyoshi N, Kimoto M. Lipopolysaccharide-binding protein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells. Int Immunol. 2010;22:271–80.CrossRefPubMed
55.
Komuro I, Keicho N, Iwamoto A, Akagawa KS. Human alveolar macrophages and granulocyte-macrophage colony-stimulating factor-induced monocyte-derived macrophages are resistant to H2O2 via their high basal and inducible levels of catalase activity. J Biol Chem. 2001;276:24360–4.CrossRefPubMed
56.
Tannheimer SL, Sorensen EA, Haran AC, Mansfield CN, Wright CD, Salmon M. Additive anti-inflammatory effects of beta 2 adrenoceptor agonists or glucocorticosteroid with roflumilast in human peripheral blood mononuclear cells. Pulm Pharmacol Ther. 2012;25:178–84.CrossRefPubMed
57.
Buenestado A, Chaumais MC, Grassin-Delyle S, Risse PA, Naline E, Longchampt E, Tenor H, Devillier P. Roflumilast inhibits lipopolysaccharide-induced tumor necrosis factor-alpha and chemokine production by human lung parenchyma. PLoS One. 2013;8:e74640.CrossRefPubMedPubMedCentral
Metadata
Title
Human lung and monocyte-derived macrophages differ with regard to the effects of β2-adrenoceptor agonists on cytokine release
Authors
Tatiana Victoni
Hélène Salvator
Charlotte Abrial
Marion Brollo
Luis Cristovão Sobrino Porto
Vincent Lagente
Emmanuel Naline
Stanislas Grassin-Delyle
Philippe Devillier
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0613-y

Other articles of this Issue 1/2017

Respiratory Research 1/2017 Go to the issue

Letter to the Editor

Chronic hypoxia aggravates monocrotaline-induced pulmonary arterial hypertension: a rodent relevant model to the human severe form of the disease

Review

Plasma and bronchoalveolar lavage samples in acute lung allograft rejection: the potential role of cytokines as diagnostic markers

Research

ABCB1 and ABCG2 drug transporters are differentially expressed in non-small cell lung cancers (NSCLC) and expression is modified by cisplatin treatment via altered Wnt signaling

Research

Involvements of p38 MAPK and oxidative stress in the ozone-induced enhancement of AHR and pulmonary inflammation in an allergic asthma model

Letter to the Editor

Asthma-COPD overlap is not a homogeneous disorder: further supporting data

Letter to the Editor

Is it possible to claim or refute sputum eosinophils ≥ 3% in asthmatics with sufficient accuracy using biomarkers?

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

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

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits