Abstract
Background: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid.
Methods: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B4 (LTB4) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) which are predominantly chemotactic for mononuclear leucocytes.
Results: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.7 and 12.2 pg/ml, respectively, p<0.01). In addition, the levels of IL-8 and neutrophil elastase-α1 protease inhibitor complex in BAL fluid were significantly correlated (r=0.65, p<0.01). There was no difference in either the release of IL-8 from cultured alveolar macrophages at 24 hours or the expression of IL-8 messenger RNA of alveolar macrophages in the two groups of current smokers with and without emphysema.
Conclusion: An accelerated response of IL-8 to chronic smoking is a factor that characterises those smokers who are susceptible to pulmonary emphysema, although the cellular source of IL-8 remains to be determined.
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Selected References
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- Baggiolini M., Dewald B., Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179. [PubMed] [Google Scholar]
- Betsuyaku T., Nishimura M., Takeyabu K., Tanino M., Venge P., Xu S., Kawakami Y. Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Am J Respir Crit Care Med. 1999 Jun;159(6):1985–1991. doi: 10.1164/ajrccm.159.6.9809043. [DOI] [PubMed] [Google Scholar]
- Betsuyaku T., Nishimura M., Yoshioka A., Takeyabu K., Miyamoto K., Kawakami Y. Elastin-derived peptides and neutrophil elastase in bronchoalveolar lavage fluid. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):720–724. doi: 10.1164/ajrccm.154.3.8810611. [DOI] [PubMed] [Google Scholar]
- Betsuyaku T., Yoshioka A., Nishimura M., Miyamoto K., Kondo T., Kawakami Y. Neutrophil elastase associated with alveolar macrophages from older volunteers. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):436–442. doi: 10.1164/ajrccm.151.2.7842203. [DOI] [PubMed] [Google Scholar]
- Burnett D., Chamba A., Hill S. L., Stockley R. A. Neutrophils from subjects with chronic obstructive lung disease show enhanced chemotaxis and extracellular proteolysis. Lancet. 1987 Nov 7;2(8567):1043–1046. doi: 10.1016/s0140-6736(87)91476-0. [DOI] [PubMed] [Google Scholar]
- Cosio M. G., Guerassimov A. Chronic obstructive pulmonary disease. Inflammation of small airways and lung parenchyma. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 2):S21–S25. doi: 10.1164/ajrccm.160.supplement_1.7. [DOI] [PubMed] [Google Scholar]
- Di Stefano A., Capelli A., Lusuardi M., Balbo P., Vecchio C., Maestrelli P., Mapp C. E., Fabbri L. M., Donner C. F., Saetta M. Severity of airflow limitation is associated with severity of airway inflammation in smokers. Am J Respir Crit Care Med. 1998 Oct;158(4):1277–1285. doi: 10.1164/ajrccm.158.4.9802078. [DOI] [PubMed] [Google Scholar]
- Gibson U. E., Heid C. A., Williams P. M. A novel method for real time quantitative RT-PCR. Genome Res. 1996 Oct;6(10):995–1001. doi: 10.1101/gr.6.10.995. [DOI] [PubMed] [Google Scholar]
- Goodman R. B., Strieter R. M., Martin D. P., Steinberg K. P., Milberg J. A., Maunder R. J., Kunkel S. L., Walz A., Hudson L. D., Martin T. R. Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):602–611. doi: 10.1164/ajrccm.154.3.8810593. [DOI] [PubMed] [Google Scholar]
- Grashoff W. F., Sont J. K., Sterk P. J., Hiemstra P. S., de Boer W. I., Stolk J., Han J., van Krieken J. M. Chronic obstructive pulmonary disease: role of bronchiolar mast cells and macrophages. Am J Pathol. 1997 Dec;151(6):1785–1790. [PMC free article] [PubMed] [Google Scholar]
- Hill A. T., Bayley D., Stockley R. A. The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Am J Respir Crit Care Med. 1999 Sep;160(3):893–898. doi: 10.1164/ajrccm.160.3.9901091. [DOI] [PubMed] [Google Scholar]
- Keatings V. M., Collins P. D., Scott D. M., Barnes P. J. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996 Feb;153(2):530–534. doi: 10.1164/ajrccm.153.2.8564092. [DOI] [PubMed] [Google Scholar]
- Koyama S., Rennard S. I., Daughton D., Shoji S., Robbins R. A. Bronchoalveolar lavage fluid obtained from smokers exhibits increased monocyte chemokinetic activity. J Appl Physiol (1985) 1991 Mar;70(3):1208–1214. doi: 10.1152/jappl.1991.70.3.1208. [DOI] [PubMed] [Google Scholar]
- Laviolette M., Coulombe R., Picard S., Braquet P., Borgeat P. Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro. J Clin Invest. 1986 Jan;77(1):54–60. doi: 10.1172/JCI112301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis R. A., Austen K. F. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest. 1984 Apr;73(4):889–897. doi: 10.1172/JCI111312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsushima K., Morishita K., Yoshimura T., Lavu S., Kobayashi Y., Lew W., Appella E., Kung H. F., Leonard E. J., Oppenheim J. J. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883–1893. doi: 10.1084/jem.167.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mio T., Romberger D. J., Thompson A. B., Robbins R. A., Heires A., Rennard S. I. Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells. Am J Respir Crit Care Med. 1997 May;155(5):1770–1776. doi: 10.1164/ajrccm.155.5.9154890. [DOI] [PubMed] [Google Scholar]
- Morrison D., Strieter R. M., Donnelly S. C., Burdick M. D., Kunkel S. L., MacNee W. Neutrophil chemokines in bronchoalveolar lavage fluid and leukocyte-conditioned medium from nonsmokers and smokers. Eur Respir J. 1998 Nov;12(5):1067–1072. doi: 10.1183/09031936.98.12051067. [DOI] [PubMed] [Google Scholar]
- Nakamura H., Fujishima S., Waki Y., Urano T., Sayama K., Sakamaki F., Terashima T., Soejima K., Tasaka S., Ishizaka A. Priming of alveolar macrophages for interleukin-8 production in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 1):1579–1586. doi: 10.1164/ajrccm.152.5.7582298. [DOI] [PubMed] [Google Scholar]
- Rankin J. A., Sylvester I., Smith S., Yoshimura T., Leonard E. J. Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan. J Clin Invest. 1990 Nov;86(5):1556–1564. doi: 10.1172/JCI114875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schnyder-Candrian S., Walz A. Neutrophil-activating protein ENA-78 and IL-8 exhibit different patterns of expression in lipopolysaccharide- and cytokine-stimulated human monocytes. J Immunol. 1997 Apr 15;158(8):3888–3894. [PubMed] [Google Scholar]
- Strieter R. M., Lukacs N. W., Standiford T. J., Kunkel S. L. Cytokines. 2. Cytokines and lung inflammation: mechanisms of neutrophil recruitment to the lung. Thorax. 1993 Jul;48(7):765–769. doi: 10.1136/thx.48.7.765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takeyabu K., Betsuyaku T., Nishimura M., Yoshioka A., Tanino M., Miyamoto K., Kawakami Y. Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Eur Respir J. 1998 Nov;12(5):1033–1039. doi: 10.1183/09031936.98.12051033. [DOI] [PubMed] [Google Scholar]
- Walz A., Burgener R., Car B., Baggiolini M., Kunkel S. L., Strieter R. M. Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8. J Exp Med. 1991 Dec 1;174(6):1355–1362. doi: 10.1084/jem.174.6.1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamaguchi E., Itoh A., Furuya K., Miyamoto H., Abe S., Kawakami Y. Release of tumor necrosis factor-alpha from human alveolar macrophages is decreased in smokers. Chest. 1993 Feb;103(2):479–483. doi: 10.1378/chest.103.2.479. [DOI] [PubMed] [Google Scholar]
- Yoshioka A., Betsuyaku T., Nishimura M., Miyamoto K., Kondo T., Kawakami Y. Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema. Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):2127–2132. doi: 10.1164/ajrccm.152.6.8520785. [DOI] [PubMed] [Google Scholar]
- de Boer W. I., Sont J. K., van Schadewijk A., Stolk J., van Krieken J. H., Hiemstra P. S. Monocyte chemoattractant protein 1, interleukin 8, and chronic airways inflammation in COPD. J Pathol. 2000 Apr;190(5):619–626. doi: 10.1002/(SICI)1096-9896(200004)190:5<619::AID-PATH555>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]