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Modulation of IL-1β, IL-6, IL-8, TNF-α, and TGF-β secretions by alveolar macrophages under NO2 exposure

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Abstract

Activated alveolar macrophages (AMs) secrete interleukine (IL)1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β), whose inflammatory and fibroblast-activating characteristics may play a role in the maintenance of pulmonary inflammatory processes and subsequent fibrosis. Human AMs were transferred to a gas cylinder and exposed to NO2 in concentrations ranging from 0.1 to 0.5 ppm in synthetic air for 30 min at 37°C. AMs were fixed on a polycarbonate membrane and placed on culture medium. A culture was established, with the exposed AM (nonstimulated or stimulated with 1 μg/ml lipopolysaccharide [LPS]), and the remaining cells were used to determine the cytokines. IL-1β, IL-6, and IL-8 were quantified by commercial enzyme-linked immunosorbent assay kits (ELISA kits). TNF-α was determined with a “sandwich” ELISA, using the biotin-streptavidin system. NO2 exposure of nonstimulated AM did not result in changes in IL-1β, IL-6, TNF-α, and TGF-β release, compared to the situation with control experiments. Exposure for 30 min to NO2 induced a significant decrease of LPS-stimulated IL-1β, IL-6, IL-8, and TNF-α (p < .05). The release of TGF-β was not significantly affected by NO2 exposure. Cytotoxicity of AM was checked by trypan blue exclusion, with values ranging from 1.3 to 3.0%. NO2 exposure of LPS-stimulated AM resulted in a functional impairment of AM after NO2 exposure regarding IL-1β, IL-6, IL-8, and TNF-α. Neither the spontaneous nor the stimulated release of TGF-β were influenced by NO2.

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References

  1. Adams JL, Czuprynski CJ (1990) Bacterial lipopolysaccharide induces release of tumor necrosis factor-α from bovine alveolar peripheral blood monocytes and alveolar macrophages in vitro. J Leukocyte Biol 48:549–556

    Google Scholar 

  2. Becker S, Madden MC, Newman SL, Devlin RB, Koren HS (1991) Modulation of human alveolar macrophage properties by ozone exposure in vitro. Toxicol Appl Pharmacol 110:403–415

    Google Scholar 

  3. Beutler B, Cerami A (1987) Cachectin: more than a tumor necrosis factor. N Engl J Med 316:379–443

    Google Scholar 

  4. Crystal RG (1991) Alveolar macrophages. In: Crystal RG, West JB, (eds) The Lung: Scientific Foundations. Raven Press, New York, 527–538

    Google Scholar 

  5. Dentener MA, Brazil V, Vonasmuth EJU, Ceska M, Buurman WA (1993) Involvement of CD14 in lipopolysaccharide induced tumor necrosis factor-alpha, IL-6 and IL-8 release by human monocytes and alveolar macrophages. J Immunol 150:2885–2891

    Google Scholar 

  6. Devlin RB, Graham DE, Koren HS (1989) Changes in RNA accumulation and protein synthesis in macrophages from humans exposed to ozone. Am Rev Respir Dis 139:A47

    Google Scholar 

  7. Dubar V, Lopez I, Gosset P, Aerts C, Voisin C, Wallaert B (1990) Mechanisms of pulmonary host defense. Agressologie 31:545–546

    Google Scholar 

  8. Elias JA, Freundlich MD, Kern JA, Rossenbloom J (1990) Cytokine networks in the regulation of inflammation and fibrosis in the lung. Chest 97:1439–1445

    Google Scholar 

  9. Foster JR, Cottrell RC, Herod IA, Atkinson HAC, Miller K(1985) A comparative study of the pulmonary effects of NO2 in the rat and hamster. Br J Exp Pathol 66:193–204

    Google Scholar 

  10. Iakovlev M, Zubairova LD, Krupnik AN, Permiakov NK (1991) Alveolar macrophages in lung physiology and pathology (editorial). Arkh Patol 53:3–8

    Google Scholar 

  11. Jörres R, Magnussen H (1991) Effect of 0.25 ppm nitrogen dioxide on the airway response to methacholine in asymptomatic asthmatic patients. Lung 169:77

    Google Scholar 

  12. Kelley J (1990) Cytokines of the lung. Am Rev Respir Dis 141:765–788

    Google Scholar 

  13. Kelley J (1990) Cytokines of the lung [comments]. Am Rev Respir Dis 141:765–788

    Google Scholar 

  14. Khalil N, Greenberg AH (1991) The role of TGF-β in pulmonary fibrosis. Ciba Found Symp 157:194–207

    Google Scholar 

  15. Kienast K, Knorst M, Lubjuhn S, Müller-Quernheim J, Ferlinz R (1994) Nitrogen dioxide-induced reactive oxygen intermediates production by human alveolar macrophages and peripheral blood mononuclear cells. Arch Environ Health 49:246–250

    Google Scholar 

  16. Kunkel SL, Standiford T, Kasahara K, Stricter RM (1991) Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp Lung Res 17:17–23

    Google Scholar 

  17. Lin G, Pearson AE, Scamurra RW, Zhou Y, Baarsch MJ, Weiss DJ, Murtaugh MP (1994) Regulation of interleukin-8 expression in porcine alveolar macrophages by bacterial lipopolysaccharide. J Biol Chem 269:77–85

    Google Scholar 

  18. Magnussen H, Jörres R (1989) Umwelt und Atemwege. Dtsch Med Wochenschr 114:1416–1420

    Google Scholar 

  19. Männel DN, Jänicke R (1989) Induction of monokine production by tumor cells. Lymphokine Res 8:257–261

    Google Scholar 

  20. Männel DN, Moore RN, Merginhagen SE (1980) Macrophages as a source of tumoricidal activity (tumor necrotizing factor). Infect Immunol 30:523–526

    Google Scholar 

  21. McCartney-Francis NL, Wahl SM (1994) Transforming growth factor-β: a matter of life and death. J Leukoc Biol 55:401–409

    Google Scholar 

  22. Mochitate K, Ishida K, Ohsumi T, Miura T (1992) Long-term effects of ozone and nitrogen dioxide on the metabolism and population of alveolar macrophages. J Toxicol Environ Health 35:247–260

    Google Scholar 

  23. Morrow PE (1984) Toxicological data on NO2: an overview. J Toxicol Environ Health 13:205–227

    Google Scholar 

  24. Mostardi RA, Woebjenberg NR, Ely DL, Conlon M, Atwood G (1981) The University of Akron study on air pollution and human health effects. II. Effects on acute respiratory illness. Arch Environ Health 36:250–255

    Google Scholar 

  25. Müller-Quernheim J, Pfeifer S, Maennel D, Strausz J, Ferlinz R (1992) Lung restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis. Am Rev Respir Dis 145:187–192

    Google Scholar 

  26. Mustafa MG, Tierney DF (1978) Biochemical and metabolic changes in the lung with oxygen, ozone and nitrogen dioxide toxicity. Am Rev Respir Dis 118:1061–1090

    Google Scholar 

  27. Nelson DJ, Jow B, Popovich KJ (1990) Whole-cell currents in macrophages: II. Alveolar macrophages. J Membr Biol 117:45–55

    Google Scholar 

  28. Polzer G, Lind I, Krüger E, Seidel A (1994) In vitro effects of nitrogen dioxide on the release of superoxide anions, TNF-α, and IL-8 by HL60-macrophages and bovine alveolar macrophages. Inhalation Toxicol 6:359–377

    Google Scholar 

  29. Polzer G, Lind I, Mosbach M, Schmidt A, Seidel A (1994) Combined influence of quartz dust, ozone and NO2 on chemotactic mobility, release of chemotactic factors and other cytokines by macrophages in vitro. Toxicol Lett 72:307–315

    Google Scholar 

  30. Sagai M, Ichinose T (1987) Lipid peroxidation and antioxidative protection mechanism in rat lungs upon acute and chronic exposure to nitrogen dioxide. Environ Health Perspect 73:179–189

    Google Scholar 

  31. Sagai M, Ichinose T, Kubota K (1984) Studies on the biochemical effects of nitrogen dioxide. Toxicol Appl Pharmacol 73:444–456

    Google Scholar 

  32. Samet JM, Marbury MC, Spengler JD (1987) Health effects and sources of indoor air pollution. Part I. Am Rev Respir Dis 136:1486–1508

    Google Scholar 

  33. Samet JM, Marbury MC, Spengler JD (1988) Health effects and sources of indoor air pollution. Part II. Am Rev Respir Dis 137:221–242

    Google Scholar 

  34. Sibille Y, Reynolds HY (1990) Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Respir Dis 141:471–501

    Google Scholar 

  35. Soukop J, Koren HS, Becker S (1993) Ozone effect on respiratory syncytial virus infectivity and cytokine production by human alveolar macrophages. Environ Res 60:178–186

    Google Scholar 

  36. Speizer FE, Ferris BJ, Bishop YMM, Sprengler JD (1980) Respiratory disease rates and pulmonary function in children associated with NO2 exposure. Am Rev Respir Dis 121:3–10

    Google Scholar 

  37. Standiford TJ, Kunkel SL, Kasahara K, Milia MJ, Rolfe MW, Stricter RM (1991) Interleukin-8 gene expression from human alveolar macrophages: the role of adherence. Am J Respir Cell Mol Biol 5:579–585

    Google Scholar 

  38. Ulich TR, Yin S, Guo K, Yi ES, Remick D, del Castillo J (1991) Intratracheal injection of endotoxin and cytokines. AJP 138:1097–1101

    Google Scholar 

  39. Ussetti P, Roca J, Augusti AGN, Montserrat JM, Rodriguez-Roisin R, Augusti-Vidal A (1984) Another asthma outbreak in Barcelona, role of oxides of nitrogen. Lancet 1:156

    Google Scholar 

  40. Voisin C, Aerts C (1984) Le macrophage alveolaire en culture en phase gazeuse, indicateur biologique en toxicologic des gaz: application à l'etude de la cytotoxicite du bioxyde d'azote (NO2). Bull Acad Natl Med 168:755–760

    Google Scholar 

  41. Voisin C, Aerts C, Fournier E, Guiselin M (1983) Alveolar macrophages versus toxic gases. A controlled in vitro approach. Curr Probl Clin Biochem 22:443–448

    Google Scholar 

  42. Voisin C, Aerts C, Houdret JL (1974) Methode d'ètude des effets du NO2 sur les macrophages alveolaires de cobaye en survie in vitro. Rev Fr Mal Resp 2:93–97

    Google Scholar 

  43. Weinberger SE, Kelman JA, Elson NA, Young RC, Reynolds HY, Fulmer JD, Crystal RG (1978)Bronchoalveolar lavage in interstitial lung disease. Ann Intern Med 89:459–486

    Google Scholar 

  44. Zabel P, Schlaak M (1993) Tumor Nekrose Faktor alpha bei Lungenerkrankungen. Pneumologie 47:49–52

    Google Scholar 

  45. Zhou D, Munster A, Winchurch RA (1991) Pathologic concentrations of interleukin 6 inhibit T cell responses via induction of activation of TGF-β. FASEB J 5:2582–2585

    Google Scholar 

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Authors and Affiliations

  1. Third Department of Internal Medicine, Division of Pneumology, Johannes Gutenberg University Hospital, Mainz

    K. Kienast, M. Knorst & R. Ferlinz

  2. Research Institut Borstel, Medical Hospital, Parkallee 35, 23845, Borstel, Federal Republic of Germany

    J. Müller-Quernheim

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  1. K. Kienast
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  2. M. Knorst
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  3. J. Müller-Quernheim
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  4. R. Ferlinz
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Kienast, K., Knorst, M., Müller-Quernheim, J. et al. Modulation of IL-1β, IL-6, IL-8, TNF-α, and TGF-β secretions by alveolar macrophages under NO2 exposure. Lung 174, 57–67 (1996). https://doi.org/10.1007/BF00167951

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