Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1982 Dec;70(6):1137–1147. doi: 10.1172/JCI110712

Activation of human complement by immunoglobulin G antigranulocyte antibody.

P K Rustagi, M S Currie, G L Logue
PMCID: PMC370330  PMID: 7174786

Abstract

The ability of antigranulocyte antibody to fix the third component of complement (C3) to the granulocyte surface was investigated by an assay that quantitates the binding of monoclonal anti-C3 antibody to paraformaldehyde-fixed cells preincubated with Felty's syndrome serum in the presence of human complement. The sera from 7 of 13 patients with Felty's syndrome bound two to three times as much C3 to granulocytes as sera from patients with uncomplicated rheumatoid arthritis. The complement-activating ability of Felty's syndrome serum seemed to reside in the monomeric IgG-containing serum fraction. For those sera capable of activating complement, the amount of C3 fixed to granulocytes was proportional to the amount of granulocyte-binding IgG present in the serum. Thus, complement fixation appeared to be a consequence of the binding of antigranulocyte antibody to the cell surface. These studies suggest a role for complement-mediated injury in the pathophysiology of immune granulocytopenia, as has been demonstrated for immune hemolytic anemia and immune thrombocytopenia.

Full text

PDF
1137

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bagby G. C., Jr T lymphocytes involved in inhibition of granulopoiesis in two neutropenic patients are of the cytotoxic/suppressor (T3+T8+) subset. J Clin Invest. 1981 Dec;68(6):1597–1600. doi: 10.1172/JCI110415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blumfelder T. M., Logue G. L., Shimm D. S. Felty's syndrome: effects of splenectomy upon granulocyte count and granulocyte-associated IgG. Ann Intern Med. 1981 May;94(5):623–628. doi: 10.7326/0003-4819-94-5-623. [DOI] [PubMed] [Google Scholar]
  3. Blumfelder T., Logue G. Human IgG antigranulocyte antibodies: comparison of detection by quantitative antiglobulin consumption and by binding of 125I staph protein A. Am J Hematol. 1981;11(1):77–84. doi: 10.1002/ajh.2830110109. [DOI] [PubMed] [Google Scholar]
  4. Borsos T., Rapp H. J. Complement fixation on cell surfaces by 19S and 7S antibodies. Science. 1965 Oct 22;150(3695):505–506. doi: 10.1126/science.150.3695.505. [DOI] [PubMed] [Google Scholar]
  5. Boxer L. A., Stossel T. P. Effects of anti-human neutrophil antibodies in vitro. Quantitative studies. J Clin Invest. 1974 Jun;53(6):1534–1545. doi: 10.1172/JCI107704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cines D. B., Passero F., Guerry D., 4th, Bina M., Dusak B., Schreiber A. D. Granulocyte-associated IgG in neutropenic disorders. Blood. 1982 Jan;59(1):124–132. [PubMed] [Google Scholar]
  7. Craddock P. R., Hammerschmidt D., White J. G., Dalmosso A. P., Jacob H. S. Complement (C5-a)-induced granulocyte aggregation in vitro. A possible mechanism of complement-mediated leukostasis and leukopenia. J Clin Invest. 1977 Jul;60(1):260–264. doi: 10.1172/JCI108763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drew S. I., Carter B. M., Guidera D., Lee K. E., Sasaki M., Terasaki P. I., Gale R. P. Further aspects of microgranulocytotoxicity. Transfusion. 1979 Jul-Aug;19(4):434–443. doi: 10.1046/j.1537-2995.1979.19479250181.x. [DOI] [PubMed] [Google Scholar]
  9. Eisner E. V., Shahidi N. T. Immune thrombocytopenia due to a drug metabolite. N Engl J Med. 1972 Aug 24;287(8):376–381. doi: 10.1056/NEJM197208242870803. [DOI] [PubMed] [Google Scholar]
  10. English D., Andersen B. R. Single-step separation of red blood cells. Granulocytes and mononuclear leukocytes on discontinuous density gradients of Ficoll-Hypaque. J Immunol Methods. 1974 Aug;5(3):249–252. doi: 10.1016/0022-1759(74)90109-4. [DOI] [PubMed] [Google Scholar]
  11. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hauch T. W., Rosse W. F. Platelet-bound complement (C3) in immune thrombocytopenia. Blood. 1977 Dec;50(6):1129–1136. [PubMed] [Google Scholar]
  13. Hurd E. R., Chubick A., Jasin H. E., Ziff M. Increased C1q binding immune complexes in Felty's syndrome: comparison with uncomplicated rheumatoid arthritis. Arthritis Rheum. 1979 Jul;22(7):697–702. doi: 10.1002/art.1780220702. [DOI] [PubMed] [Google Scholar]
  14. Lalezari P., Jiang A. F., Yegen L., Santorineou M. Chronic autoimmune neutropenia due to anti-NA2 antibody. N Engl J Med. 1975 Oct 9;293(15):744–747. doi: 10.1056/NEJM197510092931504. [DOI] [PubMed] [Google Scholar]
  15. Law S. K., Levine R. P. Interaction between the third complement protein and cell surface macromolecules. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2701–2705. doi: 10.1073/pnas.74.7.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Logue G. L., Kurlander R. J. Immunologic mechanisms of hemolysis in autoimmune hemolytic anemia. Pathobiol Annu. 1978;8:61–83. [PubMed] [Google Scholar]
  17. Logue G. L., Rosse W. F., Gockerman J. P. Measurement of the third component of complement bound to red blood cells in patients with the cold agglutinin syndrome. J Clin Invest. 1973 Feb;52(2):493–501. doi: 10.1172/JCI107206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Logue G. L., Shimm D. S. Autoimmune granulocytopenia. Annu Rev Med. 1980;31:191–200. doi: 10.1146/annurev.me.31.020180.001203. [DOI] [PubMed] [Google Scholar]
  19. Logue G. L., Silberman H. R. Felty's syndrome without splenomegaly. Am J Med. 1979 Apr;66(4):703–706. doi: 10.1016/0002-9343(79)91188-4. [DOI] [PubMed] [Google Scholar]
  20. McCallister J. A., Boxer L. A., Baehner R. L. The use and limitation of labeled staphylococcal protein A for study of antineutrophil antibodies. Blood. 1979 Dec;54(6):1330–1337. [PubMed] [Google Scholar]
  21. McCullough J., Clay M. E., Priest J. R., Jensen N. J., Lau S., Noreen H. J., Krivit W., Lalezari P. A comparison of methods for detecting leukocyte antibodies in autoimmune neutropenia. Transfusion. 1981 Sep-Oct;21(5):483–492. doi: 10.1046/j.1537-2995.1981.21582040808.x. [DOI] [PubMed] [Google Scholar]
  22. Parker C. J., Baker P. J., Rosse W. F. Increased enzymatic activity of the alternative pathway convertase when bound to the erythrocytes of paroxysmal nocturnal hemoglobinuria. J Clin Invest. 1982 Feb;69(2):337–346. doi: 10.1172/JCI110457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rochna E., Hughes-Jones N. C. The use of purified 125-I-labelled anti-gamma globulin in the determination of the number of D antigen sites on red cells of different phenotypes. Vox Sang. 1965 Nov-Dec;10(6):675–686. doi: 10.1111/j.1423-0410.1965.tb05179.x. [DOI] [PubMed] [Google Scholar]
  24. Schreiber A. D., Frank M. M. Role of antibody and complement in the immune clearance and destruction of erythrocytes. I. In vivo effects of IgG and IgM complement-fixing sites. J Clin Invest. 1972 Mar;51(3):575–582. doi: 10.1172/JCI106846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schreiber A. D., Frank M. M. Role of antibody and complement in the immune clearance and destruction of erythrocytes. II. Molecular nature of IgG and IgM complement-fixing sites and effects of their interaction with serum. J Clin Invest. 1972 Mar;51(3):583–589. doi: 10.1172/JCI106847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Slavin S., Liang M. H. Cell mediated autoimmune granulocytopenia in a case of Felty's syndrome. Ann Rheum Dis. 1980 Aug;39(4):399–402. doi: 10.1136/ard.39.4.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smit J. W., Meijer C. J., Decary F., Feltkamp-Vroom T. M. Paraformaldehyde fixation in immunofluorescence and immunoelectron microscopy. Preservation of tissue and cell surface membrane antigens. J Immunol Methods. 1974 Dec;6(1-2):93–98. doi: 10.1016/0022-1759(74)90093-3. [DOI] [PubMed] [Google Scholar]
  28. Starkebaum G., Arend W. P., Nardella F. A., Gavin S. E. Characterization of immune complexes and immunoglobulin G antibodies reactive with neutrophils in the sera of patients with Felty's syndrome. J Lab Clin Med. 1980 Aug;96(2):238–251. [PubMed] [Google Scholar]
  29. Stern M., Rosse W. F. Two populations of granulocytes in paroxysmal nocturnal hemoglobinuria. Blood. 1979 May;53(5):928–934. [PubMed] [Google Scholar]
  30. Thompson J. S., Overlin V. L., Herbick J. M., Severson C. D., Claas F. H., Amaro J. D., Burns C. P., Strauss R. G., Koepke J. A. New granulocyte antigens demonstrated by microgranulocytotoxicity assay. J Clin Invest. 1980 Jun;65(6):1431–1439. doi: 10.1172/JCI109807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Verheugt F. W., von dem Borne A. E., Décary F., Engelfriet C. P. The detection of granulocyte alloantibodies with an indirect immunofluorescence test. Br J Haematol. 1977 Aug;36(4):533–544. doi: 10.1111/j.1365-2141.1977.tb00994.x. [DOI] [PubMed] [Google Scholar]
  32. Weitzman S. A., Desmond M. C., Stossel T. P. Antigenic modulation and turnover in human neutrophils. J Clin Invest. 1979 Jul;64(1):321–325. doi: 10.1172/JCI109455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weitzman S. A., Stossel T. P. Drug-induced immunological neutropenia. Lancet. 1978 May 20;1(8073):1068–1072. doi: 10.1016/s0140-6736(78)90915-7. [DOI] [PubMed] [Google Scholar]
  34. Winkelhake J. L. Immunoglobulin structure and effector functions. Immunochemistry. 1978 Sep;15(9):695–714. doi: 10.1016/0161-5890(78)90044-5. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES