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. 2002 Aug;11(4):251–260. doi: 10.1080/096293502900000113

Interference of a short-term exposure to nitrogen dioxide with allergic airways responses to allergenic challenges in BALB/c mice.

Barbara Proust 1, Ghislaine Lacroix 1, Franck Robidel 1, Maryse Marliere 1, Anthony Lecomte 1, B Boris Vargaftig 1
PMCID: PMC1781667  PMID: 12396477

Abstract

Nitrogen dioxide (NO(2)) is a common indoor and outdoor air pollutant whose role in the induction of asthma is unclear. We investigated the effects of NO(2) on the development of asthma-like responses to allergenic challenge in BALB/c mice. Ovalbumin (OVA)-immunized mice were intranasally challenged with OVA or saline solution just before starting a 3 h exposure to 5 or 20 ppm NO(2) or air. Twenty parts per million of NO(2) induced a significant increase of bronchopulmonary hyperreactivity in OVA-challenged mice and of permeability according to the fibronectin content of the bronchoalveolar lavage fluid (BALF) 24 h after exposure, as compared with air or 5 ppm NO(2). Eosinophilia (cell counts in the BALF and eosinophil peroxidase of lung tissue) was detected at 24 and 72 h with similar levels for air and 20 ppm NO(2), whereas a marked reduction was unexpectedly observed for 5 ppm NO(2). At 24 h, interleukin-5 in the BALF was markedly reduced at 5 ppm compared with 20 ppm NO(2) and was also more intense for 20 ppm NO(2) than for the air group. In contrast to specific IgG1 titers, anti-OVA IgE titers and interleukin-4 in the BALF were not affected by NO(2) exposure. Irrespective of the concentration of NO(2), OVA-challenged mice did not develop late mucosal metaplasia compared with those exposed to OVA-air. These results indicate that a short exposure to NO(2) can exacerbate or inhibit some features of the development of allergic disease in mice and may depend on the concentration of pollutant.

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Selected References

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  1. Abehsira-Amar O., Gibert M., Joliy M., Thèze J., Jankovic D. L. IL-4 plays a dominant role in the differential development of Tho into Th1 and Th2 cells. J Immunol. 1992 Jun 15;148(12):3820–3829. [PubMed] [Google Scholar]
  2. Anderson H. R., Ponce de Leon A., Bland J. M., Bower J. S., Emberlin J., Strachan D. P. Air pollution, pollens, and daily admissions for asthma in London 1987-92. Thorax. 1998 Oct;53(10):842–848. doi: 10.1136/thx.53.10.842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bochner B. S., Undem B. J., Lichtenstein L. M. Immunological aspects of allergic asthma. Annu Rev Immunol. 1994;12:295–335. doi: 10.1146/annurev.iy.12.040194.001455. [DOI] [PubMed] [Google Scholar]
  4. Bylin G., Hedenstierna G., Lindvall T., Sundin B. Ambient nitrogen dioxide concentrations increase bronchial responsiveness in subjects with mild asthma. Eur Respir J. 1988 Jul;1(7):606–612. [PubMed] [Google Scholar]
  5. Castellsague J., Sunyer J., Sáez M., Antó J. M. Short-term association between air pollution and emergency room visits for asthma in Barcelona. Thorax. 1995 Oct;50(10):1051–1056. doi: 10.1136/thx.50.10.1051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cavanagh D. G., Morris J. B. Mucus protection and airway peroxidation following nitrogen dioxide exposure in the rat. J Toxicol Environ Health. 1987;22(3):313–328. doi: 10.1080/15287398709531074. [DOI] [PubMed] [Google Scholar]
  7. Chitano P., Hosselet J. J., Mapp C. E., Fabbri L. M. Effect of oxidant air pollutants on the respiratory system: insights from experimental animal research. Eur Respir J. 1995 Aug;8(8):1357–1371. doi: 10.1183/09031936.95.08081357. [DOI] [PubMed] [Google Scholar]
  8. Davis J. K., Davidson M. K., Schoeb T. R., Lindsey J. R. Decreased intrapulmonary killing of Mycoplasma pulmonis after short-term exposure to NO2 is associated with damaged alveolar macrophages. Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):406–411. doi: 10.1164/ajrccm/145.2_Pt_1.406. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
  11. Eum S. Y., Zuany-Amorim C., Lefort J., Pretolani M., Vargaftig B. B. Inhibition by the immunosuppressive agent FK-506 of antigen-induced airways eosinophilia and bronchial hyperreactivity in mice. Br J Pharmacol. 1997 Jan;120(1):130–136. doi: 10.1038/sj.bjp.0700860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goldstein I. F., Lieber K., Andrews L. R., Kazembe F., Foutrakis G., Huang P., Hayes C. Acute respiratory effects of short-term exposures to nitrogen dioxide. Arch Environ Health. 1988 Mar-Apr;43(2):138–142. doi: 10.1080/00039896.1988.9935842. [DOI] [PubMed] [Google Scholar]
  13. Hajela R., Janigan D. T., Landrigan P. L., Boudreau S. F., Sebastian S. Fatal pulmonary edema due to nitric acid fume inhalation in three pulp-mill workers. Chest. 1990 Feb;97(2):487–489. doi: 10.1378/chest.97.2.487. [DOI] [PubMed] [Google Scholar]
  14. Hamelmann E., Schwarze J., Takeda K., Oshiba A., Larsen G. L., Irvin C. G., Gelfand E. W. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):766–775. doi: 10.1164/ajrccm.156.3.9606031. [DOI] [PubMed] [Google Scholar]
  15. Hartert T. V., Peebles R. S., Jr Epidemiology of asthma: the year in review. Curr Opin Pulm Med. 2000 Jan;6(1):4–9. doi: 10.1097/00063198-200001000-00002. [DOI] [PubMed] [Google Scholar]
  16. Hatch G. E., Slade R., Harris L. P., McDonnell W. F., Devlin R. B., Koren H. S., Costa D. L., McKee J. Ozone dose and effect in humans and rats. A comparison using oxygen-18 labeling and bronchoalveolar lavage. Am J Respir Crit Care Med. 1994 Sep;150(3):676–683. doi: 10.1164/ajrccm.150.3.8087337. [DOI] [PubMed] [Google Scholar]
  17. Helleday R., Huberman D., Blomberg A., Stjernberg N., Sandström T. Nitrogen dioxide exposure impairs the frequency of the mucociliary activity in healthy subjects. Eur Respir J. 1995 Oct;8(10):1664–1668. doi: 10.1183/09031936.95.08101664. [DOI] [PubMed] [Google Scholar]
  18. Hubbard A. K., Vetrano K. M., Morris J. B., Thrall R. S. Acute NO2 exposure alters inflammatory cell activation and particle clearance in silica-injected mice. J Toxicol Environ Health. 1994 Mar;41(3):299–314. doi: 10.1080/15287399409531845. [DOI] [PubMed] [Google Scholar]
  19. Jenkins H. S., Devalia J. L., Mister R. L., Bevan A. M., Rusznak C., Davies R. J. The effect of exposure to ozone and nitrogen dioxide on the airway response of atopic asthmatics to inhaled allergen: dose- and time-dependent effects. Am J Respir Crit Care Med. 1999 Jul;160(1):33–39. doi: 10.1164/ajrccm.160.1.9808119. [DOI] [PubMed] [Google Scholar]
  20. Kienast K., Knorst M., Müller-Quernheim J., Ferlinz R. Modulation of IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta secretions by alveolar macrophages under NO2 exposure. Lung. 1996;174(1):57–67. doi: 10.1007/BF00167951. [DOI] [PubMed] [Google Scholar]
  21. Koren H. S. Associations between criteria air pollutants and asthma. Environ Health Perspect. 1995 Sep;103 (Suppl 6):235–242. doi: 10.1289/ehp.95103s6235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lopez A. F., Sanderson C. J., Gamble J. R., Campbell H. D., Young I. G., Vadas M. A. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med. 1988 Jan 1;167(1):219–224. doi: 10.1084/jem.167.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mohsenin V. Airway responses to 2.0 ppm nitrogen dioxide in normal subjects. Arch Environ Health. 1988 May-Jun;43(3):242–246. doi: 10.1080/00039896.1988.9934941. [DOI] [PubMed] [Google Scholar]
  24. Mohsenin V. Airway responses to nitrogen dioxide in asthmatic subjects. J Toxicol Environ Health. 1987;22(4):371–380. doi: 10.1080/15287398709531080. [DOI] [PubMed] [Google Scholar]
  25. Molfino N. A., Wright S. C., Katz I., Tarlo S., Silverman F., McClean P. A., Szalai J. P., Raizenne M., Slutsky A. S., Zamel N. Effect of low concentrations of ozone on inhaled allergen responses in asthmatic subjects. Lancet. 1991 Jul 27;338(8761):199–203. doi: 10.1016/0140-6736(91)90346-q. [DOI] [PubMed] [Google Scholar]
  26. Morgan G., Corbett S., Wlodarczyk J. Air pollution and hospital admissions in Sydney, Australia, 1990 to 1994. Am J Public Health. 1998 Dec;88(12):1761–1766. doi: 10.2105/ajph.88.12.1761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nakajima H., Iwamoto I., Tomoe S., Matsumura R., Tomioka H., Takatsu K., Yoshida S. CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am Rev Respir Dis. 1992 Aug;146(2):374–377. doi: 10.1164/ajrccm/146.2.374. [DOI] [PubMed] [Google Scholar]
  28. O'Neill C. A., van der Vliet A., Eiserich J. P., Last J. A., Halliwell B., Cross C. E. Oxidative damage by ozone and nitrogen dioxide: synergistic toxicity in vivo but no evidence of synergistic oxidative damage in an extracellular fluid. Biochem Soc Symp. 1995;61:139–152. doi: 10.1042/bss0610139. [DOI] [PubMed] [Google Scholar]
  29. Ostro B. D., Lipsett M. J., Mann J. K., Wiener M. B., Selner J. Indoor air pollution and asthma. Results from a panel study. Am J Respir Crit Care Med. 1994 Jun;149(6):1400–1406. doi: 10.1164/ajrccm.149.6.8004290. [DOI] [PubMed] [Google Scholar]
  30. Paul W. E. Interleukin-4: a prototypic immunoregulatory lymphokine. Blood. 1991 May 1;77(9):1859–1870. [PubMed] [Google Scholar]
  31. Postlethwait E. M., Bidani A. Mechanisms of pulmonary NO2 absorption. Toxicology. 1994 May 20;89(3):217–237. doi: 10.1016/0300-483x(94)90099-x. [DOI] [PubMed] [Google Scholar]
  32. Rennard S. I., Berg R., Martin G. R., Foidart J. M., Robey P. G. Enzyme-linked immunoassay (ELISA) for connective tissue components. Anal Biochem. 1980 May 1;104(1):205–214. doi: 10.1016/0003-2697(80)90300-0. [DOI] [PubMed] [Google Scholar]
  33. Robinson D. S., Hamid Q., Ying S., Tsicopoulos A., Barkans J., Bentley A. M., Corrigan C., Durham S. R., Kay A. B. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. doi: 10.1056/NEJM199201303260504. [DOI] [PubMed] [Google Scholar]
  34. Rossi O. V., Kinnula V. L., Tienari J., Huhti E. Association of severe asthma attacks with weather, pollen, and air pollutants. Thorax. 1993 Mar;48(3):244–248. doi: 10.1136/thx.48.3.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Samet J. M., Lambert W. E., Skipper B. J., Cushing A. H., Hunt W. C., Young S. A., McLaren L. C., Schwab M., Spengler J. D. Nitrogen dioxide and respiratory illnesses in infants. Am Rev Respir Dis. 1993 Nov;148(5):1258–1265. doi: 10.1164/ajrccm/148.5.1258. [DOI] [PubMed] [Google Scholar]
  36. Sandström T., Stjernberg N., Eklund A., Ledin M. C., Bjermer L., Kolmodin-Hedman B., Lindström K., Rosenhall L., Angström T. Inflammatory cell response in bronchoalveolar lavage fluid after nitrogen dioxide exposure of healthy subjects: a dose-response study. Eur Respir J. 1991 Mar;4(3):332–339. [PubMed] [Google Scholar]
  37. Sheppard L., Levy D., Norris G., Larson T. V., Koenig J. Q. Effects of ambient air pollution on nonelderly asthma hospital admissions in Seattle, Washington, 1987-1994. Epidemiology. 1999 Jan;10(1):23–30. [PubMed] [Google Scholar]
  38. Strand V., Rak S., Svartengren M., Bylin G. Nitrogen dioxide exposure enhances asthmatic reaction to inhaled allergen in subjects with asthma. Am J Respir Crit Care Med. 1997 Mar;155(3):881–887. doi: 10.1164/ajrccm.155.3.9117021. [DOI] [PubMed] [Google Scholar]
  39. Strand V., Salomonsson P., Lundahl J., Bylin G. Immediate and delayed effects of nitrogen dioxide exposure at an ambient level on bronchial responsiveness to histamine in subjects with asthma. Eur Respir J. 1996 Apr;9(4):733–740. doi: 10.1183/09031936.96.09040733. [DOI] [PubMed] [Google Scholar]
  40. Strand V., Svartengren M., Rak S., Barck C., Bylin G. Repeated exposure to an ambient level of NO2 enhances asthmatic response to a nonsymptomatic allergen dose. Eur Respir J. 1998 Jul;12(1):6–12. doi: 10.1183/09031936.98.12010006. [DOI] [PubMed] [Google Scholar]
  41. Tunnicliffe W. S., Burge P. S., Ayres J. G. Effect of domestic concentrations of nitrogen dioxide on airway responses to inhaled allergen in asthmatic patients. Lancet. 1994 Dec 24;344(8939-8940):1733–1736. doi: 10.1016/s0140-6736(94)92886-x. [DOI] [PubMed] [Google Scholar]
  42. Van Oosterhout A. J., Fattah D., Van Ark I., Hofman G., Buckley T. L., Nijkamp F. P. Eosinophil infiltration precedes development of airway hyperreactivity and mucosal exudation after intranasal administration of interleukin-5 to mice. J Allergy Clin Immunol. 1995 Jul;96(1):104–112. doi: 10.1016/s0091-6749(95)70039-0. [DOI] [PubMed] [Google Scholar]

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