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Published in: Respiratory Research 1/2014

Open Access 01-12-2014 | Research

Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD

Authors: Susan JM Hoonhorst, Wim Timens, Leo Koenderman, Adèle T Lo Tam Loi, Jan-Willem J Lammers, H Marike Boezen, Antoon JM van Oosterhout, Dirkje S Postma, Nick HT ten Hacken

Published in: Respiratory Research | Issue 1/2014

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Abstract

Background

Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age.

Methods

All participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis.

Results

Young susceptible individuals showed significantly higher increases in the expression of FcγRII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients.

Conclusions

We show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD.

Trial registration

Clinicaltrials.gov: NCT00807469
Appendix
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Literature
1.
go back to reference Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013, 187 (4): 347-365. 10.1164/rccm.201204-0596PP.PubMedCrossRef Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013, 187 (4): 347-365. 10.1164/rccm.201204-0596PP.PubMedCrossRef
2.
go back to reference van der Vaart H, Postma DS, Timens W, ten Hacken NH: Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004, 59 (8): 713-721. 10.1136/thx.2003.012468.PubMedPubMedCentralCrossRef van der Vaart H, Postma DS, Timens W, ten Hacken NH: Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004, 59 (8): 713-721. 10.1136/thx.2003.012468.PubMedPubMedCentralCrossRef
3.
go back to reference Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ, O'DONNELL WJ, Reilly JJ, Ginns L, Mentzer S, Wain J, Speizer FE: Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis. Am J Respir Crit Care Med. 1998, 157 (6 Pt 1): 1770-1778. 10.1164/ajrccm.157.6.9706014.PubMedCrossRef Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ, O'DONNELL WJ, Reilly JJ, Ginns L, Mentzer S, Wain J, Speizer FE: Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis. Am J Respir Crit Care Med. 1998, 157 (6 Pt 1): 1770-1778. 10.1164/ajrccm.157.6.9706014.PubMedCrossRef
4.
go back to reference McCloskey SC, Patel BD, Hinchliffe SJ, Reid ED, Wareham NJ, Lomas DA: Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med. 2001, 164 (8 Pt 1): 1419-1424. 10.1164/ajrccm.164.8.2105002.PubMedCrossRef McCloskey SC, Patel BD, Hinchliffe SJ, Reid ED, Wareham NJ, Lomas DA: Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med. 2001, 164 (8 Pt 1): 1419-1424. 10.1164/ajrccm.164.8.2105002.PubMedCrossRef
5.
go back to reference Hersh CP, Hokanson JE, Lynch DA, Washko GR, Make BJ, Crapo JD, Silverman EK: Family history is a risk factor for COPD. Chest. 2011, 140 (2): 343-350. 10.1378/chest.10-2761.PubMedPubMedCentralCrossRef Hersh CP, Hokanson JE, Lynch DA, Washko GR, Make BJ, Crapo JD, Silverman EK: Family history is a risk factor for COPD. Chest. 2011, 140 (2): 343-350. 10.1378/chest.10-2761.PubMedPubMedCentralCrossRef
6.
go back to reference Patel BD, Coxson HO, Pillai SG, Agusti AG, Calverley PM, Donner CF, Make BJ, Muller NL, Rennard SI, Vestbo J, Wouters EF, Hiorns MP, Nakano Y, Camp PG, Nasute Fauerbach PV, Screaton NJ, Campbell EJ, Anderson WH, Pare PD, Levy RD, Lake SL, Silverman EK, Lomas DA: Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008, 178 (5): 500-505. 10.1164/rccm.200801-059OC.PubMedCrossRef Patel BD, Coxson HO, Pillai SG, Agusti AG, Calverley PM, Donner CF, Make BJ, Muller NL, Rennard SI, Vestbo J, Wouters EF, Hiorns MP, Nakano Y, Camp PG, Nasute Fauerbach PV, Screaton NJ, Campbell EJ, Anderson WH, Pare PD, Levy RD, Lake SL, Silverman EK, Lomas DA: Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008, 178 (5): 500-505. 10.1164/rccm.200801-059OC.PubMedCrossRef
7.
go back to reference Lo Tam Loi AT, Hoonhorst SJ, Franciosi L, Bischoff R, Hoffmann RF, Heijink I, van Oosterhout AJ, Boezen HM, Timens W, Postma DS, Lammers JW, Koenderman L, Ten Hacken NH: Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study.BMJ Open 2013, 3(2). doi:10.1136/bmjopen-2012-002178. Print 2013., Lo Tam Loi AT, Hoonhorst SJ, Franciosi L, Bischoff R, Hoffmann RF, Heijink I, van Oosterhout AJ, Boezen HM, Timens W, Postma DS, Lammers JW, Koenderman L, Ten Hacken NH: Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study.BMJ Open 2013, 3(2). doi:10.1136/bmjopen-2012-002178. Print 2013.,
8.
go back to reference Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J: Standardisation of spirometry. Eur Respir J. 2005, 26 (2): 319-338. 10.1183/09031936.05.00034805.PubMedCrossRef Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J: Standardisation of spirometry. Eur Respir J. 2005, 26 (2): 319-338. 10.1183/09031936.05.00034805.PubMedCrossRef
9.
go back to reference Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G: Standardisation of the measurement of lung volumes. Eur Respir J. 2005, 26 (3): 511-522. 10.1183/09031936.05.00035005.PubMedCrossRef Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G: Standardisation of the measurement of lung volumes. Eur Respir J. 2005, 26 (3): 511-522. 10.1183/09031936.05.00035005.PubMedCrossRef
10.
go back to reference Koenderman L, Kanters D, Maesen B, Raaijmakers J, Lammers JW, de Kruif J, Logtenberg T: Monitoring of neutrophil priming in whole blood by antibodies isolated from a synthetic phage antibody library. J Leukoc Biol. 2000, 68 (1): 58-64.PubMed Koenderman L, Kanters D, Maesen B, Raaijmakers J, Lammers JW, de Kruif J, Logtenberg T: Monitoring of neutrophil priming in whole blood by antibodies isolated from a synthetic phage antibody library. J Leukoc Biol. 2000, 68 (1): 58-64.PubMed
11.
go back to reference Kato T, Kitagawa S: Regulation of neutrophil functions by proinflammatory cytokines. Int J Hematol. 2006, 84 (3): 205-209. 10.1532/IJH97.06141.PubMedCrossRef Kato T, Kitagawa S: Regulation of neutrophil functions by proinflammatory cytokines. Int J Hematol. 2006, 84 (3): 205-209. 10.1532/IJH97.06141.PubMedCrossRef
12.
go back to reference Hyun YM, Lefort CT, Kim M: Leukocyte integrins and their ligand interactions. Immunol Res. 2009, 45 (2–3): 195-208. 10.1007/s12026-009-8101-1.PubMedCrossRef Hyun YM, Lefort CT, Kim M: Leukocyte integrins and their ligand interactions. Immunol Res. 2009, 45 (2–3): 195-208. 10.1007/s12026-009-8101-1.PubMedCrossRef
13.
go back to reference Oudijk EJ, Gerritsen WB, Nijhuis EH, Kanters D, Maesen BL, Lammers JW, Koenderman L: Expression of priming-associated cellular markers on neutrophils during an exacerbation of COPD. Respir Med. 2006, 100 (10): 1791-1799. 10.1016/j.rmed.2006.01.022.PubMedCrossRef Oudijk EJ, Gerritsen WB, Nijhuis EH, Kanters D, Maesen BL, Lammers JW, Koenderman L: Expression of priming-associated cellular markers on neutrophils during an exacerbation of COPD. Respir Med. 2006, 100 (10): 1791-1799. 10.1016/j.rmed.2006.01.022.PubMedCrossRef
14.
go back to reference Blidberg K, Palmberg L, Dahlen B, Lantz AS, Larsson K: Increased neutrophil migration in smokers with or without chronic obstructive pulmonary disease. Respirology. 2012, 17 (5): 854-860. 10.1111/j.1440-1843.2012.02181.x.PubMedCrossRef Blidberg K, Palmberg L, Dahlen B, Lantz AS, Larsson K: Increased neutrophil migration in smokers with or without chronic obstructive pulmonary disease. Respirology. 2012, 17 (5): 854-860. 10.1111/j.1440-1843.2012.02181.x.PubMedCrossRef
15.
go back to reference Koethe SM, Kuhnmuench JR, Becker CG: Neutrophil priming by cigarette smoke condensate and a tobacco anti-idiotypic antibody. Am J Pathol. 2000, 157 (5): 1735-1743. 10.1016/S0002-9440(10)64810-9.PubMedPubMedCentralCrossRef Koethe SM, Kuhnmuench JR, Becker CG: Neutrophil priming by cigarette smoke condensate and a tobacco anti-idiotypic antibody. Am J Pathol. 2000, 157 (5): 1735-1743. 10.1016/S0002-9440(10)64810-9.PubMedPubMedCentralCrossRef
17.
go back to reference van der Vaart H, Postma DS, Timens W, Hylkema MN, Willemse BW, Boezen HM, Vonk JM, de Reus DM, Kauffman HF, ten Hacken NH: Acute effects of cigarette smoking on inflammation in healthy intermittent smokers. Respir Res. 2005, 6: 22-10.1186/1465-9921-6-22.PubMedPubMedCentralCrossRef van der Vaart H, Postma DS, Timens W, Hylkema MN, Willemse BW, Boezen HM, Vonk JM, de Reus DM, Kauffman HF, ten Hacken NH: Acute effects of cigarette smoking on inflammation in healthy intermittent smokers. Respir Res. 2005, 6: 22-10.1186/1465-9921-6-22.PubMedPubMedCentralCrossRef
18.
go back to reference Winkel P, Statland BE: The acute effect of cigarette smoking on the concentrations of blood leukocyte types in healthy young women. Am J Clin Pathol. 1981, 75 (6): 781-785.PubMed Winkel P, Statland BE: The acute effect of cigarette smoking on the concentrations of blood leukocyte types in healthy young women. Am J Clin Pathol. 1981, 75 (6): 781-785.PubMed
19.
go back to reference Kamp VM, Leentjens J, Pillay J, Langereis JD, de Kleijn S, Kox M, Netea MG, Pickkers P, Koenderman L: Modulation of granulocyte kinetics by GM-CSF/IFN-gamma in a human LPS rechallenge model. J Leukoc Biol. 2013, 94 (3): 513-520. 10.1189/jlb.0213066.PubMedCrossRef Kamp VM, Leentjens J, Pillay J, Langereis JD, de Kleijn S, Kox M, Netea MG, Pickkers P, Koenderman L: Modulation of granulocyte kinetics by GM-CSF/IFN-gamma in a human LPS rechallenge model. J Leukoc Biol. 2013, 94 (3): 513-520. 10.1189/jlb.0213066.PubMedCrossRef
20.
go back to reference Aoshiba K, Tamaoki J, Nagai A: Acute cigarette smoke exposure induces apoptosis of alveolar macrophages. Am J Physiol Lung Cell Mol Physiol. 2001, 281 (6): L1392-L1401.PubMed Aoshiba K, Tamaoki J, Nagai A: Acute cigarette smoke exposure induces apoptosis of alveolar macrophages. Am J Physiol Lung Cell Mol Physiol. 2001, 281 (6): L1392-L1401.PubMed
21.
go back to reference Provinciali M, Cardelli M, Marchegiani F: Inflammation, chronic obstructive pulmonary disease and aging. Curr Opin Pulm Med. 2011, 17 (Suppl 1): S3-S10. 10.1097/01.mcp.0000410742.90463.1f.PubMedCrossRef Provinciali M, Cardelli M, Marchegiani F: Inflammation, chronic obstructive pulmonary disease and aging. Curr Opin Pulm Med. 2011, 17 (Suppl 1): S3-S10. 10.1097/01.mcp.0000410742.90463.1f.PubMedCrossRef
22.
go back to reference Oudijk EJ, Lammers JW, Koenderman L: Systemic inflammation in chronic obstructive pulmonary disease. Eur Respir J Suppl. 2003, 46: 5s-13s. 10.1183/09031936.03.00004603a.PubMedCrossRef Oudijk EJ, Lammers JW, Koenderman L: Systemic inflammation in chronic obstructive pulmonary disease. Eur Respir J Suppl. 2003, 46: 5s-13s. 10.1183/09031936.03.00004603a.PubMedCrossRef
23.
go back to reference Vitalis TZ, Kern I, Croome A, Behzad H, Hayashi S, Hogg JC: The effect of latent adenovirus 5 infection on cigarette smoke-induced lung inflammation. Eur Respir J. 1998, 11 (3): 664-669.PubMed Vitalis TZ, Kern I, Croome A, Behzad H, Hayashi S, Hogg JC: The effect of latent adenovirus 5 infection on cigarette smoke-induced lung inflammation. Eur Respir J. 1998, 11 (3): 664-669.PubMed
24.
go back to reference Hulbert WC, Walker DC, Jackson A, Hogg JC: Airway permeability to horseradish peroxidase in guinea pigs: the repair phase after injury by cigarette smoke. Am Rev Respir Dis. 1981, 123 (3): 320-326.PubMed Hulbert WC, Walker DC, Jackson A, Hogg JC: Airway permeability to horseradish peroxidase in guinea pigs: the repair phase after injury by cigarette smoke. Am Rev Respir Dis. 1981, 123 (3): 320-326.PubMed
25.
go back to reference Kilburn KH, McKenzie W: Leukocyte recruitment to airways by cigarette smoke and particle phase in contrast to cytotoxicity of vapor. Science. 1975, 189 (4203): 634-637. 10.1126/science.1162344.PubMedCrossRef Kilburn KH, McKenzie W: Leukocyte recruitment to airways by cigarette smoke and particle phase in contrast to cytotoxicity of vapor. Science. 1975, 189 (4203): 634-637. 10.1126/science.1162344.PubMedCrossRef
26.
go back to reference Morrison D, Strieter RM, Donnelly SC, Burdick MD, Kunkel SL, MacNee W: Neutrophil chemokines in bronchoalveolar lavage fluid and leukocyte-conditioned medium from nonsmokers and smokers. Eur Respir J. 1998, 12 (5): 1067-1072. 10.1183/09031936.98.12051067.PubMedCrossRef Morrison D, Strieter RM, Donnelly SC, Burdick MD, Kunkel SL, MacNee W: Neutrophil chemokines in bronchoalveolar lavage fluid and leukocyte-conditioned medium from nonsmokers and smokers. Eur Respir J. 1998, 12 (5): 1067-1072. 10.1183/09031936.98.12051067.PubMedCrossRef
27.
go back to reference MacNee W, Wiggs B, Belzberg AS, Hogg JC: The effect of cigarette smoking on neutrophil kinetics in human lungs. N Engl J Med. 1989, 321 (14): 924-928. 10.1056/NEJM198910053211402.PubMedCrossRef MacNee W, Wiggs B, Belzberg AS, Hogg JC: The effect of cigarette smoking on neutrophil kinetics in human lungs. N Engl J Med. 1989, 321 (14): 924-928. 10.1056/NEJM198910053211402.PubMedCrossRef
Metadata
Title
Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD
Authors
Susan JM Hoonhorst
Wim Timens
Leo Koenderman
Adèle T Lo Tam Loi
Jan-Willem J Lammers
H Marike Boezen
Antoon JM van Oosterhout
Dirkje S Postma
Nick HT ten Hacken
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2014
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-014-0121-2

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