Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Oct;56(4):828–834. doi: 10.1172/JCI108161

Pneumococcus-induced serotonin release from human platelets. Identification of the participating plasma/serum factor as immunoglobulin.

T S Zimmerman, H L Spiegelberg
PMCID: PMC301937  PMID: 239970

Abstract

Pneumococcus-induced serotonin release from human platelets is greatly facilitated by a factor present in normal human plasma and serum. We have identified this factor as immunoglobulin by: (a) removing if from plasma and serum with solid phase antiFab antibody; (b) demonstrating its absence from the serum of an individual with severe immunoglobulin deficiency; and, (c) showing its presence in IgG preparations isolated from normal individuals. Evidence suggesting that the release reaction is triggered by pneumococcal antigen-antibody complexes rather than by nonimmune interaction of immunoglobulin with pneumococcus includes: (a) the failure of isolated IgG myeloma proteins to support release; (b) a lack of correlation between IgG concentration and "releasing factor activity" in normal human sera; (c) the identification of a normal serum that supports release by types II and III pneumococci but not type VII; and, (d) the ability of most normal sera to support release by pneumococca serotypes II and VII, though these types have not shown nonimmune reactivity with the Fc portion of the IgG molecule. The ability of antibodies present in normal serum to support pneumococcus-induced serotonin release suggests that the thrombocytopenia seen in pneumococcal infection may at least in part be caused by pneumococcal antigen-antibody complexes.

Full text

PDF
829

Selected References

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

  1. Bernheimer A. W., Schwartz L. L. Lysosomal disruption by bacterial toxins. J Bacteriol. 1964 May;87(5):1100–1104. doi: 10.1128/jb.87.5.1100-1104.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chernesky M. A., Larke R. P., Turpie A. G. Interaction between viruses and platelets: requirement of haemolytic activity for platelet aggregation induced by paramyxoviruses. J Gen Virol. 1973 Nov;21(2):205–213. doi: 10.1099/0022-1317-21-2-205. [DOI] [PubMed] [Google Scholar]
  3. Clawson C. C., White J. G. Platelet interaction with bacteria. I. Reaction phases and effects of inhibitors. Am J Pathol. 1971 Nov;65(2):367–380. [PMC free article] [PubMed] [Google Scholar]
  4. Clawson C. C., White J. G. Platelet interaction with bacteria. II. Fate of the bacteria. Am J Pathol. 1971 Nov;65(2):381–397. [PMC free article] [PubMed] [Google Scholar]
  5. Corrigan J. J., Jr Thrombocytopenia: a laboratory sign of septicemia in infants and children. J Pediatr. 1974 Aug;85(2):219–221. doi: 10.1016/s0022-3476(74)80396-3. [DOI] [PubMed] [Google Scholar]
  6. Cuatrecasas P., Wilchek M., Anfinsen C. B. Selective enzyme purification by affinity chromatography. Proc Natl Acad Sci U S A. 1968 Oct;61(2):636–643. doi: 10.1073/pnas.61.2.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Doolittle R. F., Schubert D., Schwartz S. A. Amino acid sequence studies on artiodactyl fibrinopeptides. I. Dromedary camel, mule deer, and cape buffalo. Arch Biochem Biophys. 1967 Feb;118(2):456–467. doi: 10.1016/0003-9861(67)90374-8. [DOI] [PubMed] [Google Scholar]
  8. FAHEY J. L., MCLAUGHLIN C. PREPARATION OF ANTISERA SPECIFIC FOR 6.6 S GAMMA-GLOBULINS, BETA 2A-GLOBULINS, GAMMA-1.-MACROGLOBULINS, AND FOR TYPE I AND II COMMON GAMMA-GLOBULIN DETERMINANTS. J Immunol. 1963 Oct;91:484–497. [PubMed] [Google Scholar]
  9. Forsgren A., Sjöquist J. "Protein A" from Staphylococcus aureus. 3. Reaction with rabbit gamma-globulin. J Immunol. 1967 Jul;99(1):19–24. [PubMed] [Google Scholar]
  10. HUMPHREY J. H., JAQUES R. The release of histamine and 5-hydroxytryptamine (serotonin) from platelets by antigen-antibody reactions (in vitro). J Physiol. 1955 Apr 28;128(1):9–27. doi: 10.1113/jphysiol.1955.sp005289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Henson P. M., Cochrane C. G. Immunological induction of increased vascular permeability. II. Two mechanisms of histamine release from rabbit platelets involving complement. J Exp Med. 1969 Jan 1;129(1):167–184. doi: 10.1084/jem.129.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henson P. M., Spiegelberg H. L. Release of serotonin from human platelets induced by aggregated immunoglobulins of different classes and subclasses. J Clin Invest. 1973 May;52(5):1282–1288. doi: 10.1172/JCI107296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Movat H. Z., Mustard J. F., Taichman N. S., Uriuhara T. Platelet aggregation and release of ADP, serotonin and histamine associated with phagocytosis of antigen-antibody complexes. Proc Soc Exp Biol Med. 1965 Oct;120(1):232–237. doi: 10.3181/00379727-120-30496. [DOI] [PubMed] [Google Scholar]
  14. Mueller-Eckhardt C., Lüscher E. F. Immune reactions of human blood platelets. I. A comparative study on the effects on platelets of heterologous antiplatet antiserum, antigen-antibody complexes, aggregated gammaglobulin and thrombin. Thromb Diath Haemorrh. 1968 Nov 15;20(1):155–167. [PubMed] [Google Scholar]
  15. Mustard J. F., Perry D. W., Ardlie N. G., Packham M. A. Preparation of suspensions of washed platelets from humans. Br J Haematol. 1972 Feb;22(2):193–204. doi: 10.1111/j.1365-2141.1972.tb08800.x. [DOI] [PubMed] [Google Scholar]
  16. Myllylä G., Vaheri A., Vesikari T., Penttinen K. Interaction between human blood platelets, viruses and antibodies. IV. Post-Rubella thrombocytopenic purpura and platelet aggregation by Rubella antigen-antibody interaction. Clin Exp Immunol. 1969 Mar;4(3):323–332. [PMC free article] [PubMed] [Google Scholar]
  17. Packham M. A., Nishizawa E. E., Mustard J. F. Response of platelets to tissue injury. Biochem Pharmacol. 1968 Mar;(Suppl):171–184. doi: 10.1016/0006-2952(68)90304-3. [DOI] [PubMed] [Google Scholar]
  18. Pfueller S. L., Lüscher E. F. The effects of aggregated immunoglobulins on human blood platelets in relation to their complement-fixing abilities. I. Studies of immunoglobulins of different types. J Immunol. 1972 Sep;109(3):517–525. [PubMed] [Google Scholar]
  19. Pfueller S. L., Lüscher E. F. The effects of immune complexes on blood platelets and their relationship to complement activation. Immunochemistry. 1972 Nov;9(11):1151–1165. doi: 10.1016/0019-2791(72)90085-7. [DOI] [PubMed] [Google Scholar]
  20. Reed W. P., Drach G. W., Williams R. C., Jr Antigens common to human and bacterial cells. IV. Studies of human pneumococcal disease. J Lab Clin Med. 1974 Apr;83(4):599–610. [PubMed] [Google Scholar]
  21. Riedler G. F., Straub P. W., Frick P. G. Thrombocytopenia in septicemia. A clinical study for the evaluation of its incidence and diagnostic value. Helv Med Acta. 1971 Dec;36(1):23–38. [PubMed] [Google Scholar]
  22. SPIEGELBERG H. L., WEIGLE W. O. THE CATABOLISM OF HOMOLOGOUS AND HETEROLOGOUS 7S GAMMA GLOBULIN FRAGMENTS. J Exp Med. 1965 Mar 1;121:323–338. doi: 10.1084/jem.121.3.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Seeler R. A., Metzger W., Mufson M. A. Diplococcus pneumoniae infections in children with sickle cell anemia. Am J Dis Child. 1972 Jan;123(1):8–10. doi: 10.1001/archpedi.1972.02110070058003. [DOI] [PubMed] [Google Scholar]
  24. Spiegelberg H. L., Weigle W. O. The immune response to human gamma-G-immunoglobulin in rabbits unresponsive to Fc fragment and H chain protein. J Immunol. 1967 May;98(5):1020–1027. [PubMed] [Google Scholar]
  25. Spiegelberg H. L., Weigle W. O. The production of antisera to human gammaGlobulin subclasses in rabbits using immunological unresponsiveness. J Immunol. 1968 Aug;101(2):377–380. [PubMed] [Google Scholar]
  26. Stephens C. G., Reed W. P., Kronvall G., Williams R. C., Jr Reactions between certain strains of pneumococci and Fc of IgG. J Immunol. 1974 Jun;112(6):1955–1960. [PubMed] [Google Scholar]
  27. Stossel T. P., Levy R. Intravascular coagulation associated with pneumococcal bacteremia and symmetrical peripheral gangrene. Arch Intern Med. 1970 May;125(5):876–878. [PubMed] [Google Scholar]
  28. Yoshikawa T., Tanaka K. R., Guze L. B. Infection and disseminated intravascular coagulation. Medicine (Baltimore) 1971 Jul;50(4):237–258. doi: 10.1097/00005792-197107000-00001. [DOI] [PubMed] [Google Scholar]
  29. Zucker M. B., Grant R. A., Alper C. A., Goodkofsky I., Lepow I. H. Requirement for complement components and fibrinogen in the zymosan-induced release reaction of human blood platelets. J Immunol. 1974 Dec;113(6):1744–1751. [PubMed] [Google Scholar]

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

RESOURCES