Skip to main content
SpringerLink
Log in
Book cover

Inborn Errors of Immunity and Phagocytosis pp 247–260Cite as

Chronic granulomatous disease — biochemistry with special reference to oxygen metabolism

  • Chapter

Abstract

The metabolism of oxygen by polymorphonuclear leukocytes is enormously increased in association with phagocytosis1. This oxygen consumption is not inhibited by cyanide and is largely unconnected with the respiration of these cells which contain very few mitochondria2 and derive most of their energy from glycolysis3. The oxygen is reduced and activated to form superoxide \(\left( \text O _{\dot{2}}^- \right)^4\) hydrogen peroxide (H2O2)5,6 hydroxyl radicals \(\left( \text {OH}^\cdot \right)^7\) and other reactive species which are generated in the specialized microbicidal system of neutrophils8,9.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Sbarra, A. J. and Karnovsky, M. L. (1959). The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes. J. Biol. Chem., 234, 1355

    PubMed  CAS  Google Scholar 

  2. Kirschner, R. H., Getz, G. S. and Evans, A. E. (1972). Leukocyte mitochondria: Function and biogenesis. Enzyme, 13, 56

    PubMed  CAS  Google Scholar 

  3. Selvaraj, R. J. and Sbarra, A. J. (1966). Relationship of glycolytic and oxidative metabolism to particle entry and destruction in phagocytosing cells. Nature (London), 211, 1272

    Article  CAS  Google Scholar 

  4. Babior, B. M., Kipnes, R. S. and Curnutte, J. T. (1973). Biological defence mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J. Clin. Invest., 52, 741

    Article  PubMed  CAS  Google Scholar 

  5. Iyer, G. Y. N., Islam, M. F. and Quastel, J. H. (1961). Biochemical aspects of phagocytosis. Nature (London), 192, 535

    Article  CAS  Google Scholar 

  6. Homan-Müller, J. W. T., Weening, R. S. and Roos, D. (1975). Production of hydrogen peroxide by phagocytizing human granulocytes. J. Lab. Clin. Med., 85, 198

    PubMed  Google Scholar 

  7. Tauber, A. I. and Babior, B. M. (1977). Evidence for hydroxyl radical production by human neutrophils. J. Clin. Invest., 60, 374

    Article  PubMed  CAS  Google Scholar 

  8. De Châtelet, L. R. (1975). Oxidative bactericidal mechanisms of polymorphonuclear leukocytes. J. Infect. Dis., 131, 295

    Article  Google Scholar 

  9. Klebanoff, S. J. (1975). Antimicrobial mechanisms in neutrophilic polymorphonuclear leukocytes. Semin. Hematol., 12, 117

    PubMed  CAS  Google Scholar 

  10. Mandell, G. L. (1974). Bactericidal activity of aerobic and anaerobic polymorphonuclear neutrophils. Infect. Immunol., 9, 337

    CAS  Google Scholar 

  11. Sbarra, A. J., Selvaraj, R. J., Paul, B. B., Poskitt, P. K. F., Mitchell, G. W., Louis, F. and Asbell, M. A. (1977). Granulocyte biochemistry and a hydrogen peroxide-dependent microbicidal system. In T. J. Greenwalt and G. A. Jamieson (eds.). The Granulocyte Function and Clinical Utilisation, pp. 44–48. (New York: Liss)

    Google Scholar 

  12. Weiss, S. J., King, G. W. and Lobuglio, A. F. (1977). Evidence for hydroxyl radical generation by human monocytes. Clin. Invest., 60, 370

    Article  CAS  Google Scholar 

  13. Wills, E. D. and Wilkinson, A. E. (1966). Release of enzymes from lyso- somes by irradiation and the relation of lipid peroxide formation to enzyme release. Biochem. J., 99, 657

    PubMed  CAS  Google Scholar 

  14. Berendes, H., Bridges, R. A. and Good, R. A. (1957). A fatal granuloma- tosus of childhood. The clinical study of a new syndrome. Minn. Med., 40, 309

    PubMed  CAS  Google Scholar 

  15. Holmes, B., Page, A. R. and Good, R. A. (1967). Studies of the metabolic activity of leukocytes from patients with a genetic abnormality of phagocytic function. J. Clin. Invest., 46, 1422

    Article  PubMed  CAS  Google Scholar 

  16. Holmes, B. and Good, R. A. (1971). Chronic granulomatous disease of childhood. In R. A. Good and D. W. Fisher (eds.). Immunobiology, p. 55. (Stamford: Sinauer Associates)

    Google Scholar 

  17. Holmes, B., Quie, P. G., Windhorst, D. B. and Good, R. A. (1966). Fatal granulomatous disease of childhood. An inborn abnormality of phagocytic function. Lancet, i, 1225

    Article  Google Scholar 

  18. Quie, P. G., White, J. G., Holmes, B. and Good, R. A. (1967). In vitro bactericidal capacity of human polymorphonuclear leukocytes: Diminished activity in chronic granulomatous disease of childhood. J. Clin. Invest., 46, 668

    Article  PubMed  CAS  Google Scholar 

  19. Mandell, G. L. and Hook, E. W. (1969). Leukocyte bactericidal activity in chronic granulomatous disease: correlation of bacterial hydrogen peroxide production and susceptibility to intracellular killing. J. Bacterio., 100, 531

    PubMed  CAS  Google Scholar 

  20. Body, G. P., Buckley, M., Sathey, S. and Freireich, E. J. (1966). Quantitative relationships between circulating leukocytes and infection in patients with acute leukaemia. Ann. Intern. Med., 64, 328

    Google Scholar 

  21. Windhorst, D. B., Page, A. R., Holmes, B., Quie, P. G. and Good, R. A. (1968). The pattern of genetic transmission of the leukocyte defect in fatal granulomatous disease of childhood. J. Clin. Invest., 47, 1026

    Article  PubMed  CAS  Google Scholar 

  22. Windhorst, D. B., Holmes, B. and Good, R. A. (1967). A newly defined X-linked trait in man with demonstration of the Lyon effect in carrier females. Lancet, i, 737

    Article  Google Scholar 

  23. Quie, P. G., Kaplan, E. L., Page, A. R., Gruskay, F. L. and Malawista, S. E. (1968). Defective polymorphonuclear-leukocyte function and chronic granulomatous disease in two female children. N. Engl. J. Med., 278, 976

    Article  PubMed  CAS  Google Scholar 

  24. Thompson, E. N. and Soothill, J. F. (1970). Chronic granulomatous disease: Quantitative clinicopathological relationships. Arch. Dis. Child., 45, 24

    Article  PubMed  CAS  Google Scholar 

  25. Chandra, R. K., Cope, W. A. and Soothill, J. F. (1969). Chronic granulomatous disease. Evidence for an autosomal mode of inheritance. Lancet, ii, 71

    Article  Google Scholar 

  26. Cheson, B. D., Christensen, R. L., Sperling, R., Kohler, B. E. and Babior, B. M. (1976). The origin of the chemiluminescence of phagocytosing granulocytes. J. Clin. Invest., 58, 789

    Article  PubMed  CAS  Google Scholar 

  27. Stjernholm, R. L. and Manak, R. C. (1970). Carbohydrate metabolism in leukocytes. XIV. Regulation of pentose cycle activity and glycogen metabolism during phagocytosis. J. Reticuloendothel. Soc., 8, 550

    PubMed  CAS  Google Scholar 

  28. Zatti, M. and Rossi, F. (1965). Early changes of hexose monophosphate pathway activity and of NADPH oxidation in phagocytizing leucocytes. Biochim. Biophys. Acta, 99, 557

    PubMed  CAS  Google Scholar 

  29. Reed, P. W. (1969). Glutathione and the hexose monophosphate shunt in phagocytizing and hydrogen peroxide-treated rat leukocytes. J. Biol. Chem., 244, 2459

    PubMed  CAS  Google Scholar 

  30. Nakagawara, A., Kakinuma, K., Shin, H., Miyazaki, S. and Minakami, S. (1976). Lack of cytochalasin E-induced superoxide release by polymorphonuclear leucocytes of patients with chronic granulomatous disease: a new diagnostic test. Clin. Chim. Acta, 70, 133

    Article  PubMed  CAS  Google Scholar 

  31. Repine, J. E., White, J. G., Clawson, C. C. and Holmes, B. M. (1974). Effects of phorbol myristate acetate on the metabolism and ultrastructure of neutrophils in chronic granulomatous disease. J. Clin, invest., 54, 83

    Article  CAS  Google Scholar 

  32. Baehner, R. L. and Nathan, D. G. (1968). Quantitative nitroblue tetrazolium test in chronic granulomatous disease. N. Engl.J. Med., 278, 971

    Article  PubMed  CAS  Google Scholar 

  33. Segal, A. W. and Peters, T. J. (1975). The nylon column dye test: a possible screening test of phagocyte function. Clin. Sci. Mol. Med., 49, 591

    PubMed  CAS  Google Scholar 

  34. Segal, A. W. and Levi, A. J. (1975). Cell damage and dye reduction in the quantitative nitroblue tetrazolium (NBT) test. Clin. Exp. Immunol., 19, 309

    PubMed  CAS  Google Scholar 

  35. Klebanoff, S. J. and White, L. R. (1969). Iodination defect in the leukocytes of a patient with chronic granulomatous disease of childhood. N. Engl. J. Med., 280, 460

    Article  PubMed  CAS  Google Scholar 

  36. Beck, W. S. (1958). The control of leukocyte glycolysis. J. Biol. Chem., 232, 251

    PubMed  CAS  Google Scholar 

  37. Baehner, R. L., Johnston, R. B. and Nathan, D. G. (1972). Comparative study of the metabolic and bactericidal characteristics of severely glucose- 6-phosphate dehydrogenase-deficient polymorphonuclear leukocytes and leukocytes from children with chronic granulomatous disease. J. Reticuloendothel. Soc., 12, 150

    PubMed  CAS  Google Scholar 

  38. De Chatelet, L. R., Cooper, M. R. and McCall, C. E. (1972). Stimulation of the hexose monophosphate shunt in human neutrophils by ascorbic acid: mechanism of action. Antimicrob. Agents Chemother., 1, 12

    Google Scholar 

  39. Mead, J. F. (1976). Free radical mechanisms of lipid damage and consequences for cellular membranes. In W. A. Pryor (ed.). Free Radicals in Biology, Vol. 1, pp. 51–68. (New York, San Francisco, London: Academic Press)

    Google Scholar 

  40. Gladstone, G. P. and Walton, E. (1970). Effect of iron on the bactericidal proteins from rabbit polymorphonuclear leukocytes. Nature (London), 227 849

    Article  CAS  Google Scholar 

  41. Nathan, D. G., Baehner, R. L. and Weaver, D. K. (1969). Failure of nitroblue tetrazolium reduction in the phagocytic vacuoles of leukocytes in chronic granulomatous disease. J. Clin. Invest., 48, 1895

    Article  PubMed  CAS  Google Scholar 

  42. Cagan, R. H. and Karnovsky, M. L. (1964). Enzymic basis of the respiratory stimulation during phagocytosis. Nature (London), 204, 255

    Article  CAS  Google Scholar 

  43. Segal, A. W. and Peters, T. J. (1977). Analytical subcellular fractionation of human granulocytes with special reference to the localisation of enzymes involved in microbicidal mechanisms. Clin. Sci. Mol. Med., 52, 429

    PubMed  CAS  Google Scholar 

  44. Curnutte, J. T., Karnovsky, M. L. and Babior, B. M. (1976). Manganese- dependent NADPH oxidation by granulocyte particles. J. Clin. Invest., 57, 1059

    Article  PubMed  CAS  Google Scholar 

  45. Mandell, G. L. (1970). Intraphagosomal pH of human polymorphonuclear neutrophils. Proc. Soc. Exp. Biol. Med., 134, 447

    PubMed  CAS  Google Scholar 

  46. Schiliro, G., Russo, A., Mauro, L., Pizzarelli, G. and Marino, S. (1976). Leukocyte function and characterization of leukocyte glucose-6-phosphate dehydrogenase in Sicilian mutants. Pediatr. Res., 10, 739

    PubMed  CAS  Google Scholar 

  47. Cooper, M. R., De Chatelet, L. R., McCall, C. E., La Via, M. F., Spurr, C. L. and Baehner, R. L. (1972). Complete deficiency of leukocyte glucose-6- phosphate dehydrogenase with defective bactericidal activity. J. Clin. Invest., 51, 769

    Article  PubMed  CAS  Google Scholar 

  48. Gray, G. R., Klebanoff, S. J., Stamatoyannopoulos, G., Austin, T., Naiman, S. C., Yoshida, A., Kliman, M. R. and Robinson, G. C. F. (1973). Neutrophil dysfunction, chronic granulomatous disease, and non-spherocytic haemolytic anaemia caused by complete deficiency of glucose-6-phosphate dehydrogenase. Lancet, ii, 530

    Article  Google Scholar 

  49. De Chatelet, L. R., Cooper, M. R. and McCall, C. E. (1971). Dissociation by colchicine of the hexose monophosphate shunt activation from the bactericidal activity of the leukocyte. Infect. Immunol., 3, 66

    Google Scholar 

  50. Younes, M. and Weser, U. (1976). Inhibition of nitroblue tetrazolium reduction by cuprein (superoxide dismutase), Cu(tyr)2 and Cy(lys)2. FEBS Lett., 61, 209

    Article  PubMed  CAS  Google Scholar 

  51. Wilkinson, R. W., Powars, D. R. and Hochstem, P. (1975). New evidence for the role of NADH oxidase in phagocytosis by human granulocytes. Biochem. Med., 13, 83

    Article  PubMed  CAS  Google Scholar 

  52. De Châtelet, L. R. and Shirley, P. S. (1975). Effect of nitroblue tetrazolium dye on the hexose monophosphate shunt activity of human polymorphonuclear leukocytes. Biochem. Med., 14, 391

    Article  Google Scholar 

  53. Tsan, M., Newman, B. and McIntyre, P. A. (1976). Surface sulphydryl groups and phagocytosis-associated oxidative metabolic changes in human polymorphonuclear leucocytes. Br. J. Haematol., 33, 189

    Article  PubMed  CAS  Google Scholar 

  54. Goldstein, I. M., Cerqueira, M., Lind, S. and Kaplan, H. B. (1977). Evidence that the superoxide-generating system of human leukocytes is associated with the cell surface. J. Clin. Invest., 59, 249

    Article  PubMed  CAS  Google Scholar 

  55. Weening, R. S., Roos, D., van Schaik, M. L. J., Voetman, A. A., de Boer, M. and Loos, H. A. (1977). The role of glutathione in the oxidation metabolism of phagocytic leukocytes. Studies in a family with glutathione reductase deficiency. In F. Rossi, P. L. Patriarca and D. Romeo (eds.). Movement, Metabolism and Bactericidal Mechanisms of Phagocytes, p. 277. (Padua: Piccin)

    Google Scholar 

  56. Rossi, F. and Zatti, M. (1964). Changes in the metabolic pattern of polymorphonuclear leucocytes during phagocytosis. Br. J. Exp. Pathol., 45, 548

    PubMed  CAS  Google Scholar 

  57. Rossi, F., Romeo, D. and Patriarca, P. (1972). Mechanism of phagocytosis- associated oxidative metabolism in polymorphonuclear leucocytes and macrophages. J. Reticuloendothel. Soc., 12, 127

    PubMed  CAS  Google Scholar 

  58. Hohn, D. C. and Lehrer, R. I. (1975). NADPH oxidase deficiency in X- linked chronic granulomatous disease. J. Clin. Invest., 55, 707

    Article  PubMed  CAS  Google Scholar 

  59. De Châtelet, L. R, McPhail, L. C., Mullikin, D. and McCall, C. E. (1975). An isotopic assay for NADPH oxidase activity and some characteristics of the enzyme from human polymorphonuclear leukocytes. J. Clin. Invest., 55, 714

    Article  Google Scholar 

  60. De Châtelet, L. R., McPhail, L. C. and Shirley, P. S. (1977). Effect of cyanide on NADPH oxidation by granules from human polymorphonuclear leukocytes. Blood, 49, 445

    Google Scholar 

  61. Curnutte, J. T., Kipnes, R. S. and Babior, B. M. (1975). Defect in pyridine nucleotide dependent superoxide production by a particulate fraction from the granulocytes of patients with chronic granulomatous disease. N. Engl. J. Med., 293, 628

    Article  PubMed  CAS  Google Scholar 

  62. Stossel, T. P., Mason, R. J. and Smith, A. L. (1974). Lipid peroxidation by human blood phagocytes. J. Clin. Invest., 54, 638

    Article  PubMed  CAS  Google Scholar 

  63. Baehner, R. L. and Karnovsky, M. L. (1968). Deficiency of reduced nicotinamide-adenine dinucleotide oxidase in chronic granulomatous disease. Science, 162, 1277

    Article  PubMed  CAS  Google Scholar 

  64. Segal, A. W. and Peters, T. J. (1976). Characterisation of the enzyme defect in chronic granulomatous disease. Lancet, i, 1363

    Article  Google Scholar 

  65. Segal, A. W. and Peters, T. J. (1977). Analytical subcellular fractionation of human neutrophils — The enzyme defect in chronic granulomatous disease. In F. Rossi, P. Patriarca and D. Romeo (eds.). Movement, Metabolism and Bactericidal Mechanisms of Phagocytes, p. 175. (Padua: Piccin)

    Google Scholar 

  66. Briggs, R. T., Drath, D. B., Karnovsky, M. L. and Karnovsky, M. J. (1975). Localisation of NADH oxidase on the surface of human polymorphonuclear leukocytes by a new cytochemical method. J. Cell. Biol. 67, 566

    Article  PubMed  CAS  Google Scholar 

  67. Briggs, R. T., Karnovsky, M. L. and Karnovsky, M. J. (1977). Hydrogen peroxide production in chronic granulomatous disease. J. Clin. Invest., 59, 1088

    Article  PubMed  CAS  Google Scholar 

  68. Segal, A. W., Leoni, P. and Allison, A. C. (19—). Reduced pyridine nucleotide-dependent reduction of nitroblue tetrazolium by intact neutrophils and other cells. (In preparation)

    Google Scholar 

  69. Holmes, B., Park, B. H., Malawista, S. E., Quie, P. G., Nelson, D. L. and Good, R. A. (1970). Chronic granulomatous disease in females. A deficiency of leukocyte glutathione peroxidase. N. Engl. J. Med., 283, 217

    Article  PubMed  CAS  Google Scholar 

  70. Matsuda, I., Oka, Y., Taniguchi, N., Furuyama, M., Kodama, S., Arashima, S. and Mitsuyama, T. (1976). Leukocyte glutathione peroxidase deficiency in a male child with chronic granulomatous disease. J. Pediatr., 88, 581

    Article  PubMed  CAS  Google Scholar 

  71. Rutenberg, W. D., Yang, M. C., Doberstyn, E. B. and Bellanti, J. A. (1977). Multiple leukocyte abnormalities in chronic granulomatous disease: a familial study. Pediatr. Res., 11, 158

    Article  PubMed  CAS  Google Scholar 

  72. Gold, S. B., Hanes, D. M., Stites, D. P. and Fudenberg, H. H. (1974). Abnormal kinetics of degranulation in chronic granulomatous disease. N. Engl. J. Med., 291, 332

    Article  PubMed  CAS  Google Scholar 

  73. Stossel, T. P., Root, R. K. and Vaughan, M. (1972). Phagocytosis in chronic granulomatous disease and the Chediak-Higashi syndrome. N. Engl. J. Med., 286, 120

    Article  PubMed  CAS  Google Scholar 

  74. Marsh, W. L., Øyen, R., Nichols, M. E. and Allen, F. H. (1975). Chronic granulomatous disease and the Kell blood groups. Br. J. Haematol., 29, 247

    Article  PubMed  CAS  Google Scholar 

  75. Takanaka, K. and O’Brien, P. J. (1975). Mechanisms of H2O2 formation by leukocytes. Evidence for a plasma membrane location. Arch. Biochem. Biophys., 169, 428

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. A. W. Segal
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. John F. Kennedy Institute, DK-2600, Glostrup, Denmark

    F. Güttler

  2. Department of Chemical Pathology, Institute of Child Health, WC1N 1EH, London

    J. W. T. Seakins

  3. Division of Perinatal Medicine, MRC Clinical Research Centre, Harrow, HA1 3UJ, Middlesex, London

    R. A. Harkness

Rights and permissions

Reprints and permissions

Copyright information

© 1979 The Society for the Study of Inborn Errors of Metabolism

About this chapter

Cite this chapter

Segal, A.W. (1979). Chronic granulomatous disease — biochemistry with special reference to oxygen metabolism. In: Güttler, F., Seakins, J.W.T., Harkness, R.A. (eds) Inborn Errors of Immunity and Phagocytosis. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-6197-8_17

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-6197-8_17

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-011-6199-2

  • Online ISBN: 978-94-011-6197-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation