Skip to main content
SpringerLink
Log in

Role of stimulated neutrophils from patients with systemic lupus erythematosus in tissue injury, with special reference to serum factors and increased active oxygen species generated by neutrophils

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

To examine the possible correlation between tissue injury and neutrophil produced active oxygen (AO) species in patients with systemic lupus erythematosus (SLE), we studied the capacity of the serum from six patients with untreated, active SLE to generate AO and release lysosomal enzymes by normal neutrophils. Cultured endothelial cells from human umbilical cord vein were incubated with serum-stimulated neutrophils to assess AO-induced tissue injury. Serum from patients with bacterial infections and healthy individuals served as controls. AO production was highest in the neutrophils stimulated with SLE patient-derived serum, while lysosomal enzyme release was only slightly increased. SLE neutrophils with or without stimulation and SLE serum-stimulated normal neutrophils produced significantly high levels of cytotoxicity upon coincubation with51Cr-labeled human endothelial cells. These excessive cytotoxicities were reversed by the presence of superoxide dismutase and catalase, indicating the specificity of the AO effect on endothelial cell damage. These findings suggest that tissue damage in SLE may be partially due to excessive production of AO and that both neutrophils themselves and a serum factor which activates neutrophils are involved in the mechanism for vascular injury.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fridovich, I. 1976. Oxygen radicals, hydrogen peroxide and oxygen toxicity. In Free Radicals in Biology. W. A. Pryor, editor. Academic Press, New York. 239

    Google Scholar 

  2. Salin, M. L., andJ. M. McCord. 1975. Free radicals and inflammation. Protection of phagocytosing leukocytes by superoxide dismutase.J. Clin. Invest. 56:1319–1323.

    Google Scholar 

  3. McCord, J. M., andI. Fridovich. 1978. The biology and pathology of oxygen radicals.Ann. Intern. Med. 89:122–127.

    Google Scholar 

  4. Sacks, T., C. F. Moldow, P. R. Craddock, T. K. Bowers, andH. S. Jacob. 1978. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes.J. Clin. Invest. 62:1161–1167.

    Google Scholar 

  5. Klebanoff, S. J. 1975. Antimicrobial mechanisms in neutrophilic polymorphonuclear leukocytes.Semin. Hematol. 12:117–142.

    Google Scholar 

  6. Niwa, Y., S. Miyake, T. Sakane, M. Shinou, andM. Yokoyama. 1982. Autooxidative damage in Behçet's disease-endothelial cell damage following the elevated oxygen radicals generated by stimulated neutrophils.Clin Exp. Immunol. 49:247–255.

    Google Scholar 

  7. Niwa, Y., andK. Somiya. 1984. Enhanced neutrophilic functions in mucocutaneous lymph node syndrome (MCLS)-with special reference to the possible role of increased oxygen intermediate generation in the pathogenesis of coronary thromboarteritis.J. Pediatr. 104:56–60.

    Google Scholar 

  8. Boxer, L. A., J. M. Oliver, S. P. Spielberg, J. M. Allen, B. A. Schulman, andJ. D. Schulman. 1979. Protection of granulocytes by vitamin E in glutathione synthetase deficiency.N. Engl. J. Med. 301:901–905.

    Google Scholar 

  9. Spielberg, S. P., L. A. Boxer, andL. M. Corash. 1979. Improved erythrocyte survival with high-dose vitamin E chronic hemolyzing G6PD and glutathione synthetase deficiencies.Ann. Intern. Med. 90:53–54.

    Google Scholar 

  10. Necheles, T. F., N. Maldonado, andH. Barquet-Chediak. 1969. Homozygous erythrocyte glutathione-peroxidase deficiency: Clinical and biochemical studies.Blood 33:164–169.

    Google Scholar 

  11. Skosey, J. L., D. C. Chow, S. Musinow, J. May, V. Gestautas, andY. Niwa. 1981. Effect of oxygen tension on human peripheral blood leukocytes.J. Cell Biol. 88:358–363.

    Google Scholar 

  12. Niwa, Y., T. Sakane, M. Shingu, andM. Yokoyama. 1983. Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes-a possible role of increased oxygen radicals generated by the neutrophils.J. Clin. Immunol. 3:228–240.

    Google Scholar 

  13. Niwa, Y., T. Sakane, M. Shingu, andY. Miyachi. 1984. Role of stimulated neutrophils from patients with systemic lupus erythematosus in disturbed immunoreactivity, with special reference to increased oxygen intermediates generated by the neutrophils.J. Clin. Lab. Immunol. 14:35–43.

    Google Scholar 

  14. Metzger, Z. J. T. Hoffeld, andJ. J. Oppenheim. 1980. Macrophage-mediated suppression.J. Immunol. 124:983–988.

    Google Scholar 

  15. Nishida, H., K. Tanimoto, andH. Akaoka. 1981. Effect of free radicals on the lymphocytes.Clin. Immunol. Immunopathol. 19:319–324.

    Google Scholar 

  16. Murray, H. W., andZ. A. Cohen. 1979. Macrophage oxygen-dependent antimicrobial activity. I. Susceptibility ofToxoplasma gondii to oxygen intermediates.J. Exp. Med. 150:938–949.

    Google Scholar 

  17. Murray, H. W., C. W. Juangbhnich, C. F. Nathan, andZ. A. Cohn. 1979. Macrophage oxygen-department antimicrobial activity. II. The role of oxygen intermediates.J. Exp. Med. 150:950–964.

    Google Scholar 

  18. Abramson, S. B., W. P. Given, H. S. Edelson, andG. Weissmann. 1983. Neutrphil aggregation induced by sera from patients with active systemic lupus erythematosus.Arthritis Rheum. 26:630–636.

    Google Scholar 

  19. Hashimoto, Y., M. Ziff, andE. R. Hurd. 1982. Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and Felly's syndrome sera.Arthritis Rheum. 25:1409–1418.

    Google Scholar 

  20. Stevens, M. S., H. Abbey, andL. E. Schulman. 1963. The clinical significance of extracellular material in LE cell preparation.N. Engl. J. Med. 268:976–982.

    Google Scholar 

  21. Miller, D. R., andH. G. Kaplan. 1970. Decreased nitroblue tetrazolium dye reduction in the phagocytes of patients receiving prednisone.Pediatrics 45:861–865.

    Google Scholar 

  22. Chritein, J. H., andV. F. Gragushi. 1972. Corticosteroid effect on phagocytosis and NBT reduction by human polymorphonuclear neutrophils.J. Reticuloendothel. Soc. 11:358–367.

    Google Scholar 

  23. Oyanagui, Y. 1976. Inhibition of superoxide anion production in macrophages by anti-inflammatory drugs.Biochem. Pharmacol. 25:1473–1480.

    Google Scholar 

  24. Park, B. H., S. M. Fikring, andE. M. Smithwick. 1968. Infection and nitroblue tetrazolium reduction by neutrophils. A diagnostic aid.Lancet 2:532–534.

    Google Scholar 

  25. Skosey, J. L., D. C. Chow, E. Damgaard, andL. B. Sorensen. 1973. Effect of cytochalasin B on the response of human polymorphonuclear leukocytes to zymosan.J. Cell Biol. 57:237–240.

    Google Scholar 

  26. Skosey, J. L., E. Damgaard, D. C. Chow, andL. B. Sorensen. 1974. Modification of zymosan-induced release of lysosomal enzymes from human polymorphonuclear leukocytes by cytochalasin B.J. Cell Biol. 62:625–634.

    Google Scholar 

  27. Cohen, P. P. 1957. Suspending media for normal tissues. In Monometric Techniques and Tissues Metabolism. W. W. Umbreit, editor. Burgess Publishing Co., Minneapolis, Minnesota. 149.

    Google Scholar 

  28. Jaffe, E. A., R. L. Nachman, C. G. Becker, andC. R. Kinick. 1973. Culture of human endothelial cells derived from umbilical veins.J. Clin. Invest. 52:2745–2756.

    Google Scholar 

  29. Maciag, T., G. A. Hoover, M. B. Stemerman, andR. Weinstein. 1981. Serial propagation of human endothelial cells in vitro.J. Cell Biol. 91:420–426.

    Google Scholar 

  30. Folkman, J., C. C. Haudenschild, andB. R. Zetter. 1979. Long-term culture of capillary endothelial cells.Proc. Natl. Acad. Sci. U.S.A. 76:5217–5221.

    Google Scholar 

  31. Johnson, A. R., andG. Erdos. 1977. Metabolism of vasoactive peptides by human endothelial cells in culture.J. Clin. Invest. 59:684–695.

    Google Scholar 

  32. Hoyer, L. W., R. P. Santos, andJ. R. Hoyer. 1976. Antihemophilic factor antigen. Localization in endothelial cells by immunofluorescence microscopy.J. Clin. Invest. 52:2737–2744.

    Google Scholar 

  33. Jaffe, E. A. 1976. Endothelial cells and biology of the factor 8.N. Engl. J. Med. 296:377–383.

    Google Scholar 

  34. Weissmann, G., R. B. Zurier, P. J. Spieler, andI. M. Goldstein. 1971. Mechanisms of lysosomal enzyme release from leukocytes exposed to immune complexes and other particles.J. Exp. Med. 134: 149–165.

    Google Scholar 

  35. Given, W., H. Edelson, H. Kaplan, R. Freed, andS. Abramson. 1983. Neutrophil aggregation in systemic lupus erythematosus (SLE): Evidence for a new, low-molecular-weight factor.Arthritis Rheum. 26:S12-S12.

    Google Scholar 

  36. Michelson, A. M. 1982. Oxygen radicals.Agents Actions (Suppl.) 11:179–201.

    Google Scholar 

  37. Emerit, I., andA. M. Michelson. 1981. Mechanism of photosensitivity in systemic lupus erythematosus patients.Proc. Natl. Acad. Sci. U.S.A. 78:2537–2540.

    Google Scholar 

  38. Cochrane, C. G. 1968. Immunologic tissue injury mediated by neutrophilic leukocytes.Adv. Immunol. 9:97–162.

    Google Scholar 

  39. Weissmann, G. 1972. Lysosomal mechanisms of tissue injury in arthritis.N. Engl. J. Med. 286:141–147.

    Google Scholar 

  40. Janoff, A. 1975. At least three human neutrophil lysosomal proteases are capable of degrading joint connective tissues.Ann. N. Y. Acad. Sci. 256:402–408.

    Google Scholar 

  41. Cochrane, C. G., E. R. Unanue, andF. J. Dixon. 1965. A role of polymorphonuclear leukocytes and complement in nephrotoxic nephritis.J. Exp. Med. 122:99–116.

    Google Scholar 

  42. Keystone, E. C., H. U. Schorlemmer, C. Pope, andA. C. Allison. 1977. Zymosan-induced arthritis.Arthritis Rheum. 20:1396–1401.

    Google Scholar 

  43. Gerber, D. A. 1979. Presence of an endogenous sulfhydryl inhibitor in normal serum. Subnormal levels in rheumatoid arthritis. In Proceedings of 43rd Annual Meeting of the American Rheumatism Association Section. 151.

  44. Finals, R. S., E. D. Harris, J. B. Burnett, andD. A. Gerber. 1977. Treatment of rheumatoid arthritis with L-histidine: A randomized, placebo-controlled, double-bind trial.J. Rheufmatol. 4:414–419.

    Google Scholar 

  45. Walravens, M., andJ. Dequeker. 1976. Comparison of gold orgotein treatment in rheumatoid arthritis.Ther. Res. 20:62–69.

    Google Scholar 

  46. Jhonstone, R. B., Jr., andJ. E. Lehmeyer. 1976. Elaboration of topical oxygen byproducts by neutrophils in a model of immune complex disease.J. Clin. Invest. 57:836–841.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Shimane Medical University, Japan

    Yukie Niwa & Tsuyoshi Sakane

  2. Department of Internal Medicine, Medical Institute of Bioregulation, Kyushu University, Japan

    Masao Shingu

  3. Department of Dermatology, Kyoto University, Japan

    Yoshiki Miyachi

Authors
  1. Yukie Niwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tsuyoshi Sakane
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masao Shingu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshiki Miyachi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niwa, Y., Sakane, T., Shingu, M. et al. Role of stimulated neutrophils from patients with systemic lupus erythematosus in tissue injury, with special reference to serum factors and increased active oxygen species generated by neutrophils. Inflammation 9, 163–172 (1985). https://doi.org/10.1007/BF00917588

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00917588

Keywords

Search

Navigation