Thromb Haemost 1981; 45(01): 027-033
DOI: 10.1055/s-0038-1650123
Original Article
Schattauer GmbH Stuttgart

Physiological Effects of Nonimmune Platelet Associated Immunoglobulin G

K Sugiura
The Division of Hematologic Research, The Memorial Hospital, Pawtucket, R. I., and Brown University, Providence, R. I., U.S.A
,
M Steiner
The Division of Hematologic Research, The Memorial Hospital, Pawtucket, R. I., and Brown University, Providence, R. I., U.S.A
,
M Baldini
The Division of Hematologic Research, The Memorial Hospital, Pawtucket, R. I., and Brown University, Providence, R. I., U.S.A
› Author Affiliations
Further Information

Publication History

Received 08 April 1980

Accepted 05 November 1980

Publication Date:
04 July 2018 (online)

Summary

The function of nonimmune IgG associated with platelets is unknown. In a series of experiments we have investigated this problem, relating amount of platelet-associated IgG (PAIgG) to platelet volume, serotonin release, adherence of platelets to monocytes and platelet senescence. Most of these studies were performed with human platelets. Platelets freed of preexisting PAIgG by incubation at 22° C were incubated with IgG in a series of concentrations ranging from 0.4 — 27.0 X10-6 M. The IgG preparations used were demonstrably free of aggregated forms of the protein. The amount of PAIgG bound to platelets was determined by the use of fluorescein isothiocyanate-conjugated anti-IgG antibody (F-anti-IgG antibody) which was quantified in a fluorospectrophotometer. Newly bound IgG was assayed similarly by the use of F-IgG. A dose-dependent increase in platelet volume was associated with the binding of nonimmune IgG by platelets. The process which leveled off at an IgG concentration of 1.2 —1.5 X10-5 M was almost fully reversible and was not due to platelet shape change or aggregation. Release of serotonin from IgG-treated platelets was relatively small but to the extent that it occurred was positively related to the IgG concentration to which platelets were exposed. Adherence to autologous monocytes studied quantitatively by the use of formaldehyde-fixed cells was also positively related to the amount of IgG on the platelets. Normal or IgG-defident serum had a potent inhibitory (noncompetitive) action on the binding of F-IgG and F-anti-human IgG antibody to human platelets. Cohorts of platelets prepared in rabbits during the recovery phase of immunological thrombocytopenia induced by injection of heterologous antiserum, showed an age-dependent increase of PAIgG and of IgG binding. These results suggest that PAIgG plays a role in the clearance of senescent platelets.

 
  • References

  • 1 Stossel TP. Phagocytosis: Recognition and ingestion. Semin Hematol 1975; 12: 83-116
  • 2 Oss CJ Van. Phagocytosis as a surface phenomenon. Annu Rev Microbiol 1978; 32: 19-39
  • 3 Mickenberg ID, Root RK, Wolff SM. Leukocyte function in hypogammaglobulinemia. J. Clin Invest 1970; 49: 1528-1538
  • 4 Rabinovitch M, Manejias RE, Nussenzweig V. Selective phagocytic paralysis induced by immobilized immune complexes. J Exp Med 1975; 142: 827-838
  • 5 Borne A E G KrVon Dem, Beckers D, Engelfriet CP. Mechanism of red cell destruction mediated by non-complement binding IgG antibodies: the essential role in vivo of the Fc part of IgG. Brit J Haematol 1977; 36: 485-493
  • 6 Fleer A, Meulen F WVan Der, Linthout E, Borne AEGKr Von Dem, Engelfriet CP. Destruction of IgG-sensitized erythrocytes by human blood monocytes: modulation of inhibition of IgG. Brit J Haematol 1978; 39: 425-436
  • 7 Kay MG. Mechanism of removal of senescent cells by human macrophages in situ. Proc Natl Acad Sci USA 1975; 72: 3521-3525
  • 8 Nachman RL. Platelet proteins. Semin Haematol 1968; 5: 18-31
  • 9 McMillan R, Smith RS, Longmire RI, Yelenosky R, Reid RT, Craddock CG. Immunoglobulins associated with human platelets. Blood 1971; 37: 316-322
  • 10 Dixon R, Rosse W, Ebert L. Quantitative determination of antibody in idiopathic thrombocytopenic purpura: Correlation of serum and platelet bound antibody in clinical response. New Engl J Med 1975; 292: 230-236
  • 11 Pascual CJ, Romano E. Detection of antiplatelet antibody in immune thrombocytopenic purpura. Scand J Haematol 1978; 21: 360-367
  • 12 Mueller-Eckhardt C, Mahn I, Schulz G, Mueller-Eckhardt G. Detection of platelet autoantibodies by a radioactive antiimmunoglobulin test. Vox Sang 1978; 35: 357-365
  • 13 Cines DB, Schreiber AD. Immune thrombocytopenia. Use of a Coombs antiglobulin test to detect IgG and C3 on platelets. New Eng J Med 1979; 300: 106-111
  • 14 Kelton JG, Neame PB, Bishop J, Ali M, Gauldie J, Hirsh J. The direct assay for platelet associated IgG (PAIgG): Lack of association between antibody level and platelet size. Blood 1979; 53: 73-80
  • 15 Ando Y, Steiner M, Baldini MP. Effect of chilling on membrane related functions of platelets. Transfusion 1971; 14: 453-461
  • 16 Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 1968; 21 (Suppl. 097) 77-89
  • 17 Yagi Y, Maier P, Pressman D. Two different anti-insulin antibodies in guinea pig anti-sera. J Immunology 1962; 89: 442-451
  • 18 Wood BT, Thompson SH, Goldstein G. Fluorescent antibody staining. III. Preparation of fluorescein-isothiocyanate labeled antibodies. J Immunology 1965; 95: 225-229
  • 19 Maizel JV. Acrylamide gel electrophoresis of proteins and nucleic acids. In Fundamental Techniques in Virology. Academic Press; New York and London: 1969. pp 334-362
  • 20 Sugiura K, Steiner M, Baldini M. Characterization and measurement of normal platelet associated immunoglobulin G by fluorospectrophotometry. Biochim Biophys Acta 1980; 631: 166-176
  • 21 Hirschman RJ, Shulman NR. The use of platelet serotonin release as a sensitive method for detecting anti-platelet antibodies and a plasma anti-platelet factor in patients with idiopathic thrombocytopenic purpura. Brit J Haematol 1973; 24: 793-802
  • 22 Bergmeyer HU, Bernt E, Hess B. Lactic dehydrogenase. In Methods of Enzymatic Analysis. Academic Press; New York and London: 1965. pp 736-743
  • 23 Wadsworth GP, Bryan JG. In Introduction to Probability and Random Variables. McGraw-Hill Book Company; New York: 1960
  • 24 Pfueller SL, Lüscher EF. The effect of aggregated immunoglobulins on human blood platelets in relation to their complement-fixing abilities. J Immunology 1972; 109: 517-525
  • 25 Henson P, Spiegelberg HL. Release of serotonin from human platelets induced by aggregated immunoglobulins of different classes and subclasses. J Clin Invest 1973; 52: 1282-1288
  • 26 Born GV R. Observations on the rapid morphological reaction of platelets to aggregating agents. Series Haematol 1970; 4: 114-120
  • 27 Goldberg B, Green H. The cytotoxic action of immune gamma globulin and complement on Krebs ascites tumor cells. I. Ultrastructural studies. J Exp Med 1959; a; 109: 505-510
  • 28 Goldberg B, Green H. The cytotoxic action of immune gamma globulin and complement on Krebs ascites tumor cells. II. Chemical studies. J Exp Med 1959; b; 109: 511-521
  • 29 Stossel TP. Medical progress: Phagocytosis. New Eng J Med 1974; 290: 717-723
  • 30 Pfueller SL, Weber S, Liischer EF. Studies of the mechanism of the human platelet release reaction induced by immunologic stimuli. Relationship between the binding of soluble IgG aggregates to the Fc receptor and cell response in the presence and absence of plasma. J Immunology 1977; 118: 514-524