Role of Second Messengers in Mineral Particle-Induced Production of Reactive Oxygen Species by Phagocytes

  • K. Savolainen
  • M. Ruotsalainen
Conference paper
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 17)


Exposure to asbestos has been associated for a number of years with pulmonary diseases such as pulmonary fibrosis and carcinoma. Occupational exposure to chrysotile has been a frequent cause for lung carcinoma. More recently, also an association between exposure to quartz dust and increased risk of lung carcinoma has been found (Koskela et al. 1987). Exposure to both asbestos and quartz is associated also with an increased risk of lung fibrosis.


Nitric Oxide NADPH Oxidase Alveolar Macrophage Phorbol Myristate Acetate Phosphatidic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adachi S, Kawamura K, Yoshida S, Takemoto K (1992) Oxidative damage on DNA induced by asbestos and man-made fibres in vitro. Int Arch Occup Health 63:553–557CrossRefGoogle Scholar
  2. Adamson IY, Bowden DH (1984) Relationship of alveolar epithelial injury and repair to induction of pulmonary fibrosis. Am J Pathol 130:377–383Google Scholar
  3. Baggiolini M, Boulay F, Badwey JA, Curnutte JT (1993) Activation of neutrophil leukocytes: chemoattraetant receptors and respiratory burst. FASEB J 7:1004–1010PubMedGoogle Scholar
  4. Baggiolini M, Wymann P (1990) Turning on the respiratory burst. Trends Biol Sci 15:69–72CrossRefGoogle Scholar
  5. Barnes PJ, Belvisi MG (1993) Nitric oxide and lung disease. Thorax 48:1034- 1043PubMedCrossRefGoogle Scholar
  6. Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321PubMedCrossRefGoogle Scholar
  7. Berridge MJ, Irvine RF (1989) Inositol phosphates and cell signalling. Nature 341:197–205PubMedCrossRefGoogle Scholar
  8. Chabot MC, McPhail C, Wykle RL, Kennerly AA, McCall CE (1992) Comparison of diglyceride production from choline-containing phosphoglycerides in human neutrophils stimulated with N- formylmethionyl-leucyphenylalanine, ionophore A23187 or phorbol 12-myristate 13-aeetate. Biochem J 286:693–699PubMedGoogle Scholar
  9. Chen J, Armstrong LC, Liu S, Gerriets JE, Last JA (1991) Silica increases cytosolic free calcium ion concentration of alveolar macrophages in vitro. Toxicol Appl Pharmacol 111:211–220PubMedCrossRefGoogle Scholar
  10. Cox JA, Jeng AY, Sharkey NA, Blumberg PM, Tauber AI (1985) Activation of the human neutrophil nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase by protein kinase C. J Clin Invest 76:1932–1938PubMedCrossRefGoogle Scholar
  11. Ding J, Badwey JA (1993a) Neutrophils stimulated with a chemotactic peptide or a phorbol ester exhibit different alterations in the activities of a battery of protein kinases. J Biol Chem 268:5234–5240PubMedGoogle Scholar
  12. Ding J, Badwey JA (1993b) Stimulation of neutrophils with a chemoattractant activates several novel protein kinases that can catalyze the phosphorylation of peptides derived from the 47-kDa protein component of the phagocyte oxidase and myristoylated alanine-rich C kinase substrate. J Biol Chem 268:17326–17333PubMedGoogle Scholar
  13. Doelman CJA, Leurs R, Oosterom WC, Bast A (1990) Mineral dust exposure and free radical-mediated lung damage. Exp Lung Res 16:41–55PubMedCrossRefGoogle Scholar
  14. Driscoll KE, Maurer JK, Lindenschmidt RC, Romberger D, Rennard SI, Crosby L (1990) Respiratory tract responses to dust: Relationship between dust burden, lung injury, alveolar macrophage fibronectin release, and the development of pulmonary fibrosis. Toxicol Appl Pharmacol 106:88–101PubMedCrossRefGoogle Scholar
  15. Halliwell B, Gutteridge JMC (1984) Oxygen toxicity, oxygen radicals, transition metals and diseases. Biochem J 219:1–14PubMedGoogle Scholar
  16. Hedenborg M, Klockars M (1987) Production of reactive oxygen metabolites induced by asbestos fibres in human polymorphonuclear leucocytes. J Clin Pathol 40:1189–1193PubMedCrossRefGoogle Scholar
  17. Hedenborg M, Klockars M (1989) Quartz-dust-induced production of reactive oxygen metabolites by human granulocytes. J Lung 167:23–32CrossRefGoogle Scholar
  18. Holian A, Stickle D (1985) Calcium regulation of phosphatidyl inositol turnover in macrophage activation by formyl peptides. J Cell Physiol 123:39–45PubMedCrossRefGoogle Scholar
  19. Kessels GC, Krause K-H, Verhoeven AJ (1993) Protein kinase C activity is not involved in N-formylmethionyl-leucyl-phenylalanine-induced phospholipase D activation in human neutrophils, but in essential for concomitant NADPH oxidase activation: studies with a staurosporine analogue with improved selectivity for protein kinase C. Biochem J 292:781–785PubMedGoogle Scholar
  20. Klockars M, Hedenborg M, Vanhala E (1990) Effect of two particle surface- modifying agents, polyvinylpyridine-N-oxide and carboxymethylcellulose, on the quartz and asbestos mineral fiber- induced production of reactive oxygen metabolites by human polymorphonuclear leukocytes. Arch Environ Health 45:8–14PubMedCrossRefGoogle Scholar
  21. Korchak HM, Vosshall LB, Zagon G, Ljubich P, Rich AM, Weissmann G (1988a) Activation of the neutrophil by calcium-mobilizing ligands. J Biol Chem 263:11090–11097PubMedGoogle Scholar
  22. Korchak HM, Vosshall LB, Zagon G, Ljubich P, Rich AM, Weissmann G (1988b) Activation of the neutrophil by calcium-mobilizing ligands II. Correlations of calcium, diacylglycerol, and phosphatidic acid generation with superoxide anion generation. J Biol Chem 263:11098- 11105PubMedGoogle Scholar
  23. Koskela R-S, Klockars M, Jarvinen E, Kolari PJ, Rossi A (1987) Cancer mortality of granite workers. Scand J Work Environ Health 13:26–31PubMedCrossRefGoogle Scholar
  24. Lad PM, Kaptein JS, Lin C-KE, Kalunta CI, Scott SJ, Gu DG (1992) G- proteins and the role of second messengers in the regulation of the human neutrophil. Immunol Ser 57:107–136PubMedGoogle Scholar
  25. Lugano EM, Dauber JH, Daniele RP (1982) Acute experimental silicosis. Lung morphology, histology, and macrophage chemotaxin secretion. Am J Pathol 109:27–36PubMedGoogle Scholar
  26. Meshulam T, Diamond RD, Lyman CA, Wysong DR, Melnick DA (1988) Temporal association of calcium mobilization, inositol trisphosphate generation, and superoxide anion release by human neutrophils activated by serum opsonized and nonopsonized particulate stimuli. Biochem Biophys Res Commun 150:532–539PubMedCrossRefGoogle Scholar
  27. Mitsuyama T, Takeshige K, Minakami S (1993) Phosphatidic acids induces the respiratory burst of electropermeabilized human neutrophils by acting on a downstream step of protein kinase C. FEBS Lett 328:67–70PubMedCrossRefGoogle Scholar
  28. Moncada S, Higgs A (1993) The L-argine-nitric oxide pathway. New Engl J Med 329:2002–2012PubMedCrossRefGoogle Scholar
  29. Mossman BT, Gee JBL (1989) Asbestos-related diseases. New Engl J Med 320:1921CrossRefGoogle Scholar
  30. Mossman BT, Light W, Wei E (1983) Asbestos: Mechanisms of toxicity and carcinogenicity in the respiratory tract. Ann Rev Pharmacol Toxicol 23:595–615CrossRefGoogle Scholar
  31. Mossman BT, March JP (1989) Evidence supporting a role for active oxygen species in asbestos induced toxicity and lung disease. Env Health Perspect 81:91–94CrossRefGoogle Scholar
  32. Nishizuka Y (1986) The role of protein kinase C in cell surface signal transduction and tumor promotion. Science 233:305–312PubMedCrossRefGoogle Scholar
  33. Nyberg P, Klockars M (1990a) Measurement of reactive oxygen metabolites produced by human monocyte-derived macrophages exposed to mineral dusts. Int J Exp Path 71:537–544Google Scholar
  34. Nyberg P, Klockars M (1990b) Quartz-induced production of reactive oxygen metabolites by activated human monocyte-derived macrophages. APMIS 98:823–827PubMedCrossRefGoogle Scholar
  35. Nyberg P, Klockars M (1990c) Effect of immunoglobulins on mineral dust- induced production of reactive oxygen metabolites by human macrophages. Inflammation 14:621–629PubMedCrossRefGoogle Scholar
  36. Putney JW Jr (1993) Excitement about calcium signalling in inexcitable cells. Science 262:676–678PubMedCrossRefGoogle Scholar
  37. Rojanasakul Y, Wang L, Malanga CJ, Ma JYC, Banks DE, Ma JKH (1993) Altered calcium homeostasis and cell injury in silica-exposed alveolar macrophages. J Cell Phys 154:310–316CrossRefGoogle Scholar
  38. Roney PL, Holian A (1989) Possible mechanism of chrysotile asbestos- stimulated superoxide anion production in guinea pig alveolar macrophages. Toxicol Appl Pharmacol 100:132–144PubMedCrossRefGoogle Scholar
  39. Ruotsalainen M, Savolainen K (1994) Effects of a protein kinase C inhibitor, Ro 31–7549, on the activation of human leukocytes by particulate stimuli. Hum Exper Toxicol (in Press)Google Scholar
  40. Sadler KL, Badwey JA (1988) Second messengers involved in superoxide production byneutrophils. Hemat Oncol Clin North Am 2:185–200Google Scholar
  41. Salamino F, Sparatore B, De Tullio, Mengotti P, Melloni E, Pontremoli S (1991) Respiratory burst in activated neutrophils is directly correlated to the intracellular level of protein kinase C. Eur J Biochem 200:573- 577PubMedCrossRefGoogle Scholar
  42. Seifert R, Schultz G (1991) The superoxide-forming NADPH oxidase of phagocytes: an enzyme system regulated by multiple mechanism. Reviews of Physiology, Biochemistry, and Pharmacology 117, Springer-Verlag, Heidelberg, p. 19Google Scholar
  43. Troll W, Wiesner R (1985) The Role of Oxygen Radicals as a Possible Mechanism of Tumor Promotion. Annu Rev Pharmacol Toxicol 25:509–528PubMedCrossRefGoogle Scholar
  44. von Tscharner V, Prod’hom B, Baggiolini M, Reuter H (1986) Ion channels in human neutrophils activated by a rise in free cytosolic calcium concentration. Nature 324:369–372CrossRefGoogle Scholar
  45. Tuomala M, Hirvonen M-R, Holopainen M, Savolainen K (1993a) Stimulation of human poly morphonuclear leukocytes by consecutive doses of quartz and interactions of quartz with fMLP. Toxicol Appl Pharmacol 118:224–232PubMedCrossRefGoogle Scholar
  46. Tuomala MH, Hirvonen M-R, Savolainen KM (1992) Production of inositol phosphates and reactive oxygen metabolites in quartz-dust-stimulated human polymorphonuclear leukocytes. FEBS Lett 296:57–60PubMedCrossRefGoogle Scholar
  47. Tuomala M, Hirvonen M R, Savolainen KM (1993b) Changes in free intracellular calcium and production of reactive oxygen metabolites in human leukocytes by soluble and particulate stimuli. Toxicology 80:71–82PubMedCrossRefGoogle Scholar
  48. Twomey B. Muid RE, Nixon JS, Sedwick AD, Wilkonson SE, Dale MM (1990) The effect of new potent selective inhibitors of protein kinase C on the neutrophil respiratory burst. Biochem Biophys Res Commun 171:1087–1092PubMedCrossRefGoogle Scholar
  49. Umei T, Ohhara N, Okamura S, Harada M, Nakao M, Shirai T, Niho Y (1993) Activation of neutrophils NADPH oxidase by PMA: cytosol activity is translocated in phorbol-primed neutrophils. Int J Biochem 25:631–633PubMedCrossRefGoogle Scholar
  50. Wright CD, Miilsch A, Busse R, Osswal H (1989) Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun 160:813- 819PubMedCrossRefGoogle Scholar
  51. Yano E (1988) Mineral fiber-induced malondialdehyde formation and effect of oxidant scavengers in phagocytic cells. Int Arch Occup Environ Health 61:19–23PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • K. Savolainen
    • 1
    • 2
  • M. Ruotsalainen
    • 2
  1. 1.Department of ToxicologyNational Public Health InstituteFinland
  2. 2.Department of Environmental SciencesUniversity of KuopioKuopioFinland

Personalised recommendations