Role of Nitric Oxide Radicals in Asbestos-Induced Injury

  • George Thomas
  • Tasuke Ando
  • Kiran Verma
  • Elliott Kagan
Conference paper
Part of the NATO ASI Series book series (volume 85)


It is well recognized that inhalation of asbestos fibers is linked to the causation of a variety of clinical disorders including interstitial pulmonary fibrosis, parietal pleural plaques, bronchogenic carcinoma and diffuse malignant mesothelioma of the pleura and peritoneum (Kagan, 1985; Mossman and Gee, 1989). Although the pathogenesis of these diseases has not been elucidated fully, there is evidence that alveolar macrophages (AM) play a pivotal role in mediating asbestos-related injury. Thus, studies in asbestosexposed rodents and in asbestos workers have shown that AM are recruited to the sites of deposition of inhaled asbestos fibers (Kagan, 1988; Rom et al., 1991). It has also been demonstrated that asbestos fibres can activate AM to secrete a diverse group of inflammatory mediators including cytokine growth factors, chemoattractants and arachidonic acid metabolites (Kagan, 1988; Rom, et al., 1991). Several studies also have demonstrated that the in vitro phagocytic uptake of asbestos fibers can generate a variety of reactive oxygen species (ROS) such as the superoxide anion \((O_2^{* - })\), the hydroxyl radical (OH*) and hydrogen peroxide (Shull, et al., 1992; Mossman, et al., 1986). It also has been reported that scavengers of oxygen free radicals, such as superoxide dismutase (SOD) and catalase, may ameliorate the injurious effects of asbestos exposure (Mossman, et al,. 1986; Mossman, et al,. 1990). These studies are predicated on \((O_2^{* - })\)-driven, iron-catalyzed, Fenton-Haber-Weiss reactions which generate the OH* radical (Grisham, 1992), and suggest that ROS may have an important role in the pathobiology of asbestos-related disease.


Alveolar Macrophage Carbonyl Iron Asbestos Exposure Asbestos Fiber Carbonyl Iron Particle 
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  1. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87: 1620–1624PubMedCrossRefGoogle Scholar
  2. Brody AR (1993) Asbestos-induced lung disease. Environ Hlth Perspect 100: 21–30CrossRefGoogle Scholar
  3. Grisham MB (1992) Reactive Metabolites of Oxygen and Nitrogen in Biology and Medicine. R.G. Landes Co., Austin, TexasGoogle Scholar
  4. Ignarro U (1990) Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 30: 535–560PubMedCrossRefGoogle Scholar
  5. Jorens PG, Van Overveld FJ, Bult H, Vermeire PA, and Herman AG (1991) Larginine- dependent production of nitrogen oxides by rat pulmonary macrophages. Eur J Pharmacol 200: 205–209PubMedCrossRefGoogle Scholar
  6. Kagan E (1985) Current perspectives in asbestosis. Ann Allergy 54: 464–473PubMedGoogle Scholar
  7. Kagan E (1988) Current issues regarding the pathobiology of asbestosis: a chronologic perspective. J Thorac Imaging 3 (4): 1–9PubMedCrossRefGoogle Scholar
  8. Kiechle FL, Malinski T (1993) Nitric oxide. Biochemistry, pathophysiology, and detection. Am J Clin Pathol 100: 567–575Google Scholar
  9. Kourembanas S, McQuillan LP, Leung GK, Faller DV (1993) Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia. J Clin Invest 92: 99–104PubMedCrossRefGoogle Scholar
  10. Lund LG, Aust AE (1992) Iron mobilization from crocidolite asbestos greatly enhances crocidolite-dependent formation of DNA single-strand breaks in phi X174 RFI DNA. Carcinogenesis 13: 637–642PubMedCrossRefGoogle Scholar
  11. Miller K, Kagan E (1977) Immune adherence reactivity of rat alveolar macrophages following inhalation of crocidolite asbestos. Clin Exp Immunol 29: 152–158PubMedGoogle Scholar
  12. Moncada S, Higgs EA (1991) Endogenous nitric oxide: physiology, pathology and clinical relevance. Eur J Clin Invest 21: 361–374PubMedCrossRefGoogle Scholar
  13. Mossman BT, Gee JBL (1989) Asbestos-related diseases. N Engl J Med 320: 1721–1730PubMedCrossRefGoogle Scholar
  14. Mossman BT, Marsh JP, Sesko A, Hill S, Shatos MA, Doherty J, Petruska JGoogle Scholar
  15. Adler KB, Hemenway D, Mickey R, Vacek P, Kagan E (1990) Inhibition of lung injury, inflammation and interstitial pulmonary fibrosis by polyethylene glycol-conjugated catalase in a rapid inhalational model of asbestosis. Am Rev Respir Dis 141: 1266–1261PubMedGoogle Scholar
  16. Mossman BT, Marsh JP, Shatos MA (1986) Alteration of superoxide dismutase activity in tracheal epithelial cells by asbestos and inhibition of cytotoxicity by antioxidants. Lab Invest 54: 204–212PubMedGoogle Scholar
  17. Mulligan MS, Hevel JM, Marietta MA, Ward PA (1991) Tissue injury caused by deposition of immune complexes is L-arginine dependent. Proc Natl Acad Sci USA 88: 6338–6342PubMedCrossRefGoogle Scholar
  18. Nguyen T, Branson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR (1992) DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 89: 3030–3034PubMedCrossRefGoogle Scholar
  19. Nussler AK, Billiar TR (1993) Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol 54: 171–178PubMedGoogle Scholar
  20. O’Connor KJ, Knowles RG, Patel KD (1991) Nitrovasodilators have proliferative as well as antiproliferative effects. J Cardiovasc Pharmacol 17 (Suppl): S100–S103CrossRefGoogle Scholar
  21. Pryor WA (1986) Oxy-radicals and related species: their formation, lifetimes, and reactions. Annu Rev Physiol 48: 657–667PubMedCrossRefGoogle Scholar
  22. Radi R, Beckman JS, Bush KM, Freeman BA (1991) Peroxynitrite oxidation of sulfhydryls. J Biol Chem 266: 4244–4250PubMedGoogle Scholar
  23. Reif DW, Simmons RD (1990) Nitric oxide mediates iron release from ferritin. Arch Biochem Biophys 283: 537–541PubMedCrossRefGoogle Scholar
  24. Robinson, BWS, Rose AH, Hayes A, Musk AW (1988) Increased pulmonary gamma interferon production in asbestosis. Am Rev Respir Dis 138: 278–283PubMedGoogle Scholar
  25. Rom WN, Travis WD (1992) Lymphocyte-macrophage alveolitis in nonsmoking individuals occupationally exposed to asbestos. Chest 101: 779–786PubMedCrossRefGoogle Scholar
  26. Rom WN, Travis WD, Brody AR (1991) Cellular and molecular basis of the asbestos-related diseases. Am Rev Respir Dis 143: 408–422PubMedGoogle Scholar
  27. Rubanyi GM, Vanhoutte PM (1986) Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol 250: H822–H827PubMedGoogle Scholar
  28. Seekamp A, Mulligan MS, Till GO, Ward PA (1993) Requirements for neutrophil products and L-arginine in ischemia-reperfusion injury. Am J Pathol 142: 1217–1226PubMedGoogle Scholar
  29. Shull S, Manohar M, Marsh JP, Janssen YMW, Mossman BT (1992) Role of iron and reactive oxygen species in asbestos-induced lung injury. In: Moslen MT, Smith CV (eds) Free Radical Mechanisms of Tissue Injury. CRC Press, Boca Raton pp 153–162Google Scholar
  30. Thomas G, Ramwell PW (1986) Induction of vascular relaxation by hydroperoxides. Biochem Biophys Res Commun 139: 102–108PubMedCrossRefGoogle Scholar
  31. Thomas G, Ramwell PW (1988) Vasodilatory properties of mono-L-argininecontaining compounds. Biochem Biophys Res Commun 154: 332–338PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • George Thomas
    • 2
  • Tasuke Ando
    • 1
  • Kiran Verma
    • 1
  • Elliott Kagan
    • 1
  1. 1.Departments of PathologyGeorgetown University School of MedicineN.W.USA
  2. 2.Physiology & BiophysicsGeorgetown University School of MedicineN.W.USA

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