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. 2003 Feb;58(2):135–142. doi: 10.1136/thorax.58.2.135

Relationship between inflammatory cells and structural changes in the lungs of asymptomatic and never smokers: a biopsy study

K Amin 1, A Ekberg-Jansson 1, C Lofdahl 1, P Venge 1
PMCID: PMC1746573  PMID: 12554896

Abstract

Methods: Bronchial biopsy specimens were taken from 29 smokers and 16 never smokers and stained with monoclonal antibodies HNL, EPO, AA1, CD68 in order to identify neutrophils, eosinophils, mast cells, and macrophages, respectively. The biopsy specimens were also stained with monoclonal antibodies to the cytokines interleukin (IL)-1ß and IL-8. Structural changes were identified by staining the biopsy specimens with antibodies to tenascin and laminin and by evaluating the condition of the epithelial layer.

Results: The numbers of all inflammatory cells and of cytokine staining cells were significantly increased in smokers. The thickness of the tenascin and laminin layers was increased in the smoking group and the integrity of the epithelial layer was significantly reduced. In smokers the epithelial integrity was negatively correlated with the number of eosinophils and macrophages. The thickness of the tenascin and laminin layers was positively correlated with AA1 and EPO positive cells only.

Conclusion: High numbers of inflammatory cells are present in the bronchial mucosa of asymptomatic smokers which have a clear relationship with the impaired epithelial integrity. The increased thickness of the laminin and tenascin layers in these subjects was strongly related to the presence of eosinophils and mast cells, suggesting a role for these cells in tissue remodelling of the airways of smokers.

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Selected References

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  1. Altraja A., Laitinen A., Virtanen I., Kämpe M., Simonsson B. G., Karlsson S. E., Håkansson L., Venge P., Sillastu H., Laitinen L. A. Expression of laminins in the airways in various types of asthmatic patients: a morphometric study. Am J Respir Cell Mol Biol. 1996 Oct;15(4):482–488. doi: 10.1165/ajrcmb.15.4.8879182. [DOI] [PubMed] [Google Scholar]
  2. Amin K., Lúdvíksdóttir D., Janson C., Nettelbladt O., Björnsson E., Roomans G. M., Boman G., Sevéus L., Venge P. Inflammation and structural changes in the airways of patients with atopic and nonatopic asthma. BHR Group. Am J Respir Crit Care Med. 2000 Dec;162(6):2295–2301. doi: 10.1164/ajrccm.162.6.9912001. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Dinarello C. A. Interleukin-1 and interleukin-1 antagonism. Blood. 1991 Apr 15;77(8):1627–1652. [PubMed] [Google Scholar]
  5. Ekberg-Jansson A., Andersson B., Bake B., Boijsen M., Enanden I., Rosengren A., Skoogh B. E., Tylén U., Venge P., Löfdahl C. G. Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT. Respir Med. 2001 May;95(5):363–373. doi: 10.1053/rmed.2001.1050. [DOI] [PubMed] [Google Scholar]
  6. Ekberg-Jansson A., Arvå E., Nilsson O., Löfdahl C. G., Andersson B. A comparison of the expression of lymphocyte activation markers in blood, bronchial biopsies and bronchoalveolar lavage: evidence for an enrichment of activated T lymphocytes in the bronchoalveolar space. Respir Med. 1999 Aug;93(8):563–570. doi: 10.1016/s0954-6111(99)90156-7. [DOI] [PubMed] [Google Scholar]
  7. Gleich G. J., Flavahan N. A., Fujisawa T., Vanhoutte P. M. The eosinophil as a mediator of damage to respiratory epithelium: a model for bronchial hyperreactivity. J Allergy Clin Immunol. 1988 May;81(5 Pt 1):776–781. doi: 10.1016/0091-6749(88)90931-1. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Hargreave F. E., Leigh R. Induced sputum, eosinophilic bronchitis, and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 2):S53–S57. doi: 10.1164/ajrccm.160.supplement_1.14. [DOI] [PubMed] [Google Scholar]
  10. Haslam P. L., Turton C. W., Lukoszek A., Salsbury A. J., Dewar A., Collins J. V., Turner-Warwick M. Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy. Thorax. 1980 May;35(5):328–339. doi: 10.1136/thx.35.5.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hernnäs J., Särnstrand B., Lindroth P., Peterson C. G., Venge P., Malmström A. Eosinophil cationic protein alters proteoglycan metabolism in human lung fibroblast cultures. Eur J Cell Biol. 1992 Dec;59(2):352–363. [PubMed] [Google Scholar]
  12. Jeffery P. K. Differences and similarities between chronic obstructive pulmonary disease and asthma. Clin Exp Allergy. 1999 Jun;29 (Suppl 2):14–26. [PubMed] [Google Scholar]
  13. Kampf C., Relova A. J., Sandler S., Roomans G. M. Effects of TNF-alpha, IFN-gamma and IL-beta on normal human bronchial epithelial cells. Eur Respir J. 1999 Jul;14(1):84–91. doi: 10.1034/j.1399-3003.1999.14a15.x. [DOI] [PubMed] [Google Scholar]
  14. Laitinen A., Altraja A., Kämpe M., Linden M., Virtanen I., Laitinen L. A. Tenascin is increased in airway basement membrane of asthmatics and decreased by an inhaled steroid. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):951–958. doi: 10.1164/ajrccm.156.3.9610084. [DOI] [PubMed] [Google Scholar]
  15. Lams B. E., Sousa A. R., Rees P. J., Lee T. H. Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1518–1523. doi: 10.1164/ajrccm.158.5.9802121. [DOI] [PubMed] [Google Scholar]
  16. Lams B. E., Sousa A. R., Rees P. J., Lee T. H. Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease. Eur Respir J. 2000 Mar;15(3):512–516. doi: 10.1034/j.1399-3003.2000.15.14.x. [DOI] [PubMed] [Google Scholar]
  17. Linden M., Rasmussen J. B., Piitulainen E., Tunek A., Larson M., Tegner H., Venge P., Laitinen L. A., Brattsand R. Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis. Am Rev Respir Dis. 1993 Nov;148(5):1226–1232. doi: 10.1164/ajrccm/148.5.1226. [DOI] [PubMed] [Google Scholar]
  18. Luomanen M., Tiitta O., Heikinheimo K., Leimola-Virtanen R., Heinaro I., Happonen R. P. Effect of snuff and smoking on tenascin expression in oral mucosa. J Oral Pathol Med. 1997 Aug;26(7):334–338. doi: 10.1111/j.1600-0714.1997.tb00225.x. [DOI] [PubMed] [Google Scholar]
  19. McCachren S. S., Lightner V. A. Expression of human tenascin in synovitis and its regulation by interleukin-1. Arthritis Rheum. 1992 Oct;35(10):1185–1196. doi: 10.1002/art.1780351011. [DOI] [PubMed] [Google Scholar]
  20. Motojima S., Frigas E., Loegering D. A., Gleich G. J. Toxicity of eosinophil cationic proteins for guinea pig tracheal epithelium in vitro. Am Rev Respir Dis. 1989 Mar;139(3):801–805. doi: 10.1164/ajrccm/139.3.801. [DOI] [PubMed] [Google Scholar]
  21. O'Shaughnessy T. C., Ansari T. W., Barnes N. C., Jeffery P. K. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. Am J Respir Crit Care Med. 1997 Mar;155(3):852–857. doi: 10.1164/ajrccm.155.3.9117016. [DOI] [PubMed] [Google Scholar]
  22. Oxhøj H., Bake B. Measurement of closing volume with the single breath nitrogen method. Scand J Respir Dis. 1974;55(6):320–331. [PubMed] [Google Scholar]
  23. Pesci A., Rossi G. A., Bertorelli G., Aufiero A., Zanon P., Olivieri D. Mast cells in the airway lumen and bronchial mucosa of patients with chronic bronchitis. Am J Respir Crit Care Med. 1994 May;149(5):1311–1316. doi: 10.1164/ajrccm.149.5.8173772. [DOI] [PubMed] [Google Scholar]
  24. Quanjer P. H., Tammeling G. J., Cotes J. E., Pedersen O. F., Peslin R., Yernault J. C. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5–40. [PubMed] [Google Scholar]
  25. Robinson B. W., Venaille T., Blum R., Mendis A. H. Eosinophils and major basic protein damage but do not detach human amniotic epithelial cells. Exp Lung Res. 1992 Sep-Oct;18(5):583–593. doi: 10.3109/01902149209031696. [DOI] [PubMed] [Google Scholar]
  26. Rosengren A., Orth-Gomér K., Wedel H., Wilhelmsen L. Stressful life events, social support, and mortality in men born in 1933. BMJ. 1993 Oct 30;307(6912):1102–1105. doi: 10.1136/bmj.307.6912.1102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saetta M., Baraldo S., Corbino L., Turato G., Braccioni F., Rea F., Cavallesco G., Tropeano G., Mapp C. E., Maestrelli P. CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Aug;160(2):711–717. doi: 10.1164/ajrccm.160.2.9812020. [DOI] [PubMed] [Google Scholar]
  28. Saetta M., Di Stefano A., Maestrelli P., Turato G., Ruggieri M. P., Roggeri A., Calcagni P., Mapp C. E., Ciaccia A., Fabbri L. M. Airway eosinophilia in chronic bronchitis during exacerbations. Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 1):1646–1652. doi: 10.1164/ajrccm.150.6.7952628. [DOI] [PubMed] [Google Scholar]
  29. Saetta M., Turato G., Baraldo S., Zanin A., Braccioni F., Mapp C. E., Maestrelli P., Cavallesco G., Papi A., Fabbri L. M. Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):1016–1021. doi: 10.1164/ajrccm.161.3.9907080. [DOI] [PubMed] [Google Scholar]
  30. Saetta M., Turato G., Maestrelli P., Mapp C. E., Fabbri L. M. Cellular and structural bases of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 May;163(6):1304–1309. doi: 10.1164/ajrccm.163.6.2009116. [DOI] [PubMed] [Google Scholar]
  31. Salorinne Y. Single-breath pulmonary diffusing capacity. Reference values and application in connective tissue diseases and in various lung diseases. Scand J Respir Dis Suppl. 1976;96:1–84. [PubMed] [Google Scholar]
  32. Salpeter Shelley R., Ormiston Thomas M., Salpeter Edwin E. Cardioselective beta-blockers in patients with reactive airway disease: a meta-analysis. Ann Intern Med. 2002 Nov 5;137(9):715–725. doi: 10.7326/0003-4819-137-9-200211050-00035. [DOI] [PubMed] [Google Scholar]
  33. Sevéus L., Amin K., Peterson C. G., Roomans G. M., Venge P. Human neutrophil lipocalin (HNL) is a specific granule constituent of the neutrophil granulocyte. Studies in bronchial and lung parenchymal tissue and peripheral blood cells. Histochem Cell Biol. 1997 May;107(5):423–432. doi: 10.1007/s004180050129. [DOI] [PubMed] [Google Scholar]
  34. Sixt R., Bake B., Oxhöj H. The single-breath N2-test and spirometry in healthy non-smoking males. Eur J Respir Dis. 1984 May;65(4):296–304. [PubMed] [Google Scholar]
  35. Traber M. G., van der Vliet A., Reznick A. Z., Cross C. E. Tobacco-related diseases. Is there a role for antioxidant micronutrient supplementation? Clin Chest Med. 2000 Mar;21(1):173-87, x. doi: 10.1016/s0272-5231(05)70016-2. [DOI] [PubMed] [Google Scholar]
  36. Turato G., Di Stefano A., Maestrelli P., Mapp C. E., Ruggieri M. P., Roggeri A., Fabbri L. M., Saetta M. Effect of smoking cessation on airway inflammation in chronic bronchitis. Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 1):1262–1267. doi: 10.1164/ajrccm.152.4.7551380. [DOI] [PubMed] [Google Scholar]
  37. Venge P., Dahl R., Fredens K., Peterson C. G. Epithelial injury by human eosinophils. Am Rev Respir Dis. 1988 Dec;138(6 Pt 2):S54–S57. doi: 10.1164/ajrccm/138.6_Pt_2.S54. [DOI] [PubMed] [Google Scholar]
  38. Wong D. T., Donoff R. B., Yang J., Song B. Z., Matossian K., Nagura N., Elovic A., McBride J., Gallagher G., Todd R. Sequential expression of transforming growth factors alpha and beta 1 by eosinophils during cutaneous wound healing in the hamster. Am J Pathol. 1993 Jul;143(1):130–142. [PMC free article] [PubMed] [Google Scholar]
  39. Xaubet A., Agustí C., Luburich P., Barberá J. A., Carrión M., Ayuso M. C., Roca J., Rodriguez-Roisin R. Interleukin-8 expression in bronchoalveolar lavage cells in the evaluation of alveolitis in idiopathic pulmonary fibrosis. Respir Med. 1998 Feb;92(2):338–344. doi: 10.1016/s0954-6111(98)90118-4. [DOI] [PubMed] [Google Scholar]

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