Abstract
Background: Repeated daily exposure of healthy human subjects to NO2 induces an acute airway inflammatory response characterised by neutrophil influx in the bronchial mucosa
Aims: To assess the expression of NF-κB, cytokines, and ICAM-1 in the bronchial epithelium.
Methods: Twelve healthy, young non-smoking volunteers were exposed to 2 ppm of NO2/filtered air (four hours/day) for four successive days on separate occasions. Fibreoptic bronchoscopy was performed one hour after air and final NO2 exposures. Bronchial biopsy specimens were immunostained for NF-κB, TNF-α, eotaxin, Gro-α, GM-CSF, IL-5, -6, -8, -10, -13, and ICAM-1 and their expression was quantified using computerised image analysis.
Results: Expression of IL-5, IL-10, IL-13, and ICAM-1 increased following NO2 exposure.
Conclusion: Upregulation of the Th2 cytokines suggests that repeated exposure to NO2 has the potential to exert a "pro-allergic" effect on the bronchial epithelium. Upregulation of ICAM-1 highlights an underlying mechanism for leucocyte influx, and could also explain the predisposition to respiratory tract viral infections following NO2 exposure since ICAM-1 is a major receptor for rhino and respiratory syncytial viruses.
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- Bianco A., Sethi S. K., Allen J. T., Knight R. A., Spiteri M. A. Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1. Eur Respir J. 1998 Sep;12(3):619–626. doi: 10.1183/09031936.98.12030619. [DOI] [PubMed] [Google Scholar]
- Blomberg A., Krishna M. T., Bocchino V., Biscione G. L., Shute J. K., Kelly F. J., Frew A. J., Holgate S. T., Sandström T. The inflammatory effects of 2 ppm NO2 on the airways of healthy subjects. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):418–424. doi: 10.1164/ajrccm.156.2.9612042. [DOI] [PubMed] [Google Scholar]
- Blomberg A., Krishna M. T., Helleday R., Söderberg M., Ledin M. C., Kelly F. J., Frew A. J., Holgate S. T., Sandström T. Persistent airway inflammation but accommodated antioxidant and lung function responses after repeated daily exposure to nitrogen dioxide. Am J Respir Crit Care Med. 1999 Feb;159(2):536–543. doi: 10.1164/ajrccm.159.2.9711068. [DOI] [PubMed] [Google Scholar]
- Bonfield T. L., Konstan M. W., Burfeind P., Panuska J. R., Hilliard J. B., Berger M. Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregulated in cystic fibrosis. Am J Respir Cell Mol Biol. 1995 Sep;13(3):257–261. doi: 10.1165/ajrcmb.13.3.7544594. [DOI] [PubMed] [Google Scholar]
- Britten K. M., Howarth P. H., Roche W. R. Immunohistochemistry on resin sections: a comparison of resin embedding techniques for small mucosal biopsies. Biotech Histochem. 1993 Sep;68(5):271–280. doi: 10.3109/10520299309105629. [DOI] [PubMed] [Google Scholar]
- Cassatella M. A., Meda L., Bonora S., Ceska M., Constantin G. Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. J Exp Med. 1993 Dec 1;178(6):2207–2211. doi: 10.1084/jem.178.6.2207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devalia J. L., Campbell A. M., Sapsford R. J., Rusznak C., Quint D., Godard P., Bousquet J., Davies R. J. Effect of nitrogen dioxide on synthesis of inflammatory cytokines expressed by human bronchial epithelial cells in vitro. Am J Respir Cell Mol Biol. 1993 Sep;9(3):271–278. doi: 10.1165/ajrcmb/9.3.271. [DOI] [PubMed] [Google Scholar]
- Devalia J. L., Sapsford R. J., Cundell D. R., Rusznak C., Campbell A. M., Davies R. J. Human bronchial epithelial cell dysfunction following in vitro exposure to nitrogen dioxide. Eur Respir J. 1993 Oct;6(9):1308–1316. [PubMed] [Google Scholar]
- Fiorentino D. F., Zlotnik A., Mosmann T. R., Howard M., O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991 Dec 1;147(11):3815–3822. [PubMed] [Google Scholar]
- Gardner D. E. Oxidant-induced enhanced sensitivity to infection in animal models and their extrapolations to man. J Toxicol Environ Health. 1984;13(2-3):423–439. doi: 10.1080/15287398409530508. [DOI] [PubMed] [Google Scholar]
- Greve J. M., Davis G., Meyer A. M., Forte C. P., Yost S. C., Marlor C. W., Kamarck M. E., McClelland A. The major human rhinovirus receptor is ICAM-1. Cell. 1989 Mar 10;56(5):839–847. doi: 10.1016/0092-8674(89)90688-0. [DOI] [PubMed] [Google Scholar]
- Hamelmann E., Gelfand E. W. Role of IL-5 in the development of allergen-induced airway hyperresponsiveness. Int Arch Allergy Immunol. 1999 Sep;120(1):8–16. doi: 10.1159/000024215. [DOI] [PubMed] [Google Scholar]
- Humbert M., Durham S. R., Kimmitt P., Powell N., Assoufi B., Pfister R., Menz G., Kay A. B., Corrigan C. J. Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. J Allergy Clin Immunol. 1997 May;99(5):657–665. doi: 10.1016/s0091-6749(97)70028-9. [DOI] [PubMed] [Google Scholar]
- Krutmann J., Köck A., Schauer E., Parlow F., Möller A., Kapp A., Förster E., Schöpf E., Luger T. A. Tumor necrosis factor beta and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression. J Invest Dermatol. 1990 Aug;95(2):127–131. doi: 10.1111/1523-1747.ep12477839. [DOI] [PubMed] [Google Scholar]
- Matsuzaki Z., Okamoto Y., Sarashina N., Ito E., Togawa K., Saito I. Induction of intercellular adhesion molecule-1 in human nasal epithelial cells during respiratory syncytial virus infection. Immunology. 1996 Aug;88(4):565–568. doi: 10.1046/j.1365-2567.1996.d01-687.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melia R. J., Florey C. D., Altman D. G., Swan A. V. Association between gas cooking and respiratory disease in children. Br Med J. 1977 Jul 16;2(6080):149–152. doi: 10.1136/bmj.2.6080.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melia R. J., Florey C. V., Chinn S. The relation between respiratory illness in primary schoolchildren and the use of gas for cooking--I. Results from a national survey. Int J Epidemiol. 1979 Dec;8(4):333–338. doi: 10.1093/ije/8.4.333. [DOI] [PubMed] [Google Scholar]
- Montefort S., Holgate S. T., Howarth P. H. Leucocyte-endothelial adhesion molecules and their role in bronchial asthma and allergic rhinitis. Eur Respir J. 1993 Jul;6(7):1044–1054. [PubMed] [Google Scholar]
- Mustafa M. G., Tierney D. F. Biochemical and metabolic changes in the lung with oxygen, ozone, and nitrogen dioxide toxicity. Am Rev Respir Dis. 1978 Dec;118(6):1061–1090. doi: 10.1164/arrd.1978.118.6.1061. [DOI] [PubMed] [Google Scholar]
- Nakazawa M., Sugi N., Kawaguchi H., Ishii N., Nakajima H., Minami M. Predominance of type 2 cytokine-producing CD4+ and CD8+ cells in patients with atopic dermatitis. J Allergy Clin Immunol. 1997 May;99(5):673–682. doi: 10.1016/s0091-6749(97)70030-7. [DOI] [PubMed] [Google Scholar]
- Salvi S., Semper A., Blomberg A., Holloway J., Jaffar Z., Papi A., Teran L., Polosa R., Kelly F., Sandström T. Interleukin-5 production by human airway epithelial cells. Am J Respir Cell Mol Biol. 1999 May;20(5):984–991. doi: 10.1165/ajrcmb.20.5.3463. [DOI] [PubMed] [Google Scholar]
- Shardonofsky F. R., Venzor J., 3rd, Barrios R., Leong K. P., Huston D. P. Therapeutic efficacy of an anti-IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma. J Allergy Clin Immunol. 1999 Jul;104(1):215–221. doi: 10.1016/s0091-6749(99)70138-7. [DOI] [PubMed] [Google Scholar]
- Staunton D. E., Merluzzi V. J., Rothlein R., Barton R., Marlin S. D., Springer T. A. A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses. Cell. 1989 Mar 10;56(5):849–853. doi: 10.1016/0092-8674(89)90689-2. [DOI] [PubMed] [Google Scholar]
- Takanashi S., Hasegawa Y., Kanehira Y., Yamamoto K., Fujimoto K., Satoh K., Okamura K. Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers. Eur Respir J. 1999 Aug;14(2):309–314. doi: 10.1034/j.1399-3003.1999.14b12.x. [DOI] [PubMed] [Google Scholar]
- Van der Pouw Kraan T. C., Van der Zee J. S., Boeije L. C., De Groot E. R., Stapel S. O., Aarden L. A. The role of IL-13 in IgE synthesis by allergic asthma patients. Clin Exp Immunol. 1998 Jan;111(1):129–135. doi: 10.1046/j.1365-2249.1998.00471.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhu Z., Homer R. J., Wang Z., Chen Q., Geba G. P., Wang J., Zhang Y., Elias J. A. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999 Mar;103(6):779–788. doi: 10.1172/JCI5909. [DOI] [PMC free article] [PubMed] [Google Scholar]