Immunoglobulin G is a Platelet Alpha Granule-secreted Protein

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1985 Nov 1

PMID 2932474

Citations 20

Authors

J N George

S Saucerman

S P Levine

L K Knieriem

D F BAINTON

Affiliations

Soon will be listed here.

Abstract

It has been known for 27 yr that blood platelets contain IgG, yet its subcellular location and significance have never been clearly determined. In these studies, the location of IgG within human platelets was investigated by immunocytochemical techniques and by the response of platelet IgG to agents that cause platelet secretion. Using frozen thin-sections of platelets and an immunogold probe, IgG was located within the alpha-granules. Thrombin stimulation caused parallel secretion of platelet IgG and two known alpha-granule proteins, platelet factor 4 and beta-thromboglobulin, beginning at 0.02 U/ml and reaching 100% at 0.5 U/ml. Thrombin-induced secretion of all three proteins was inhibited by prostaglandin E1 and dibutyryl-cyclic AMP. Calcium ionophore A23187 also caused parallel secretion of all three proteins, whereas ADP caused virtually no secretion of any of the three. From these data and a review of the literature, we hypothesize that plasma IgG is taken up by megakaryocytes and delivered to the alpha-granules, where it is stored for later secretion by mature platelets.

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References

Davey M, LUSCHER E . Actions of thrombin and other coagulant and proteolytic enzymes on blood platelets. Nature. 1967; 216(5118):857-8. DOI: 10.1038/216857a0. View

Salmon J . [Immuno-electrophoresis of human blood platelet antigens]. Schweiz Med Wochenschr. 1958; 88(42):1047-9. View

McMillan R, Smith R, Longmire R, Yelenosky R, Reid R, CRADDOCK C . Immunoglobulins associated with human platelets. Blood. 1971; 37(3):316-22. View

Mustard J, Perry D, Ardlie N, Packham M . Preparation of suspensions of washed platelets from humans. Br J Haematol. 1972; 22(2):193-204. DOI: 10.1111/j.1365-2141.1972.tb08800.x. View

McMillan R, Longmire R, Yelenosky R, Lang J, Heath V, CRADDOCK C . Immunoglobulin synthesis by human lymphoid tissues: normal bone marrow as a major site of IgG production. J Immunol. 1972; 109(6):1386-94. View

Natvig J, KUNKEL H . Human immunoglobulins: classes, subclasses, genetic variants, and idiotypes. Adv Immunol. 1973; 16:1-59. DOI: 10.1016/s0065-2776(08)60295-3. View

Dixon R, ROSSE W, Ebbert L . Quantitative determination of antibody in idiopathic thrombocytopenic purpura. Correlation of serum and platelet-bound antibody with clinical response. N Engl J Med. 1975; 292(5):230-6. DOI: 10.1056/NEJM197501302920503. View

Mustard J, Perry D, Kinlough-Rathbone R, Packham M . Factors responsible for ADP-induced release reaction of human platelets. Am J Physiol. 1975; 228(6):1757-65. DOI: 10.1152/ajplegacy.1975.228.6.1757. View

Luiken G, McMillan R, Lightsey A, Gordon P, Zevely S, Schulman I . Platelet-associated IgG in immune thrombocytopenic purpura. Blood. 1977; 50(2):317-25. View

10.

Nachman R, Levine R, Jaffe E . Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. J Clin Invest. 1977; 60(4):914-21. PMC: 372440. DOI: 10.1172/JCI108846. View

11.

Levine S, Krentz L . Development of a radioimmunoassay for human platelet factor 4. Thromb Res. 1977; 11(5):673-86. DOI: 10.1016/0049-3848(77)90025-1. View

12.

George J . Studies on platelet plasma membranes. IV. Quantitative analysis of platelet membrane glycoproteins by (125I)-diazotized diiodosulfanilic acid labeling and SDS-polyacrylamide gel electrophoresis. J Lab Clin Med. 1978; 92(3):430-46. View

13.

Lichtman M, Chamberlain J, Simon W, Santillo P . Parasinusoidal location of megakaryocytes in marrow: a determinant of platelet release. Am J Hematol. 1978; 4(4):303-12. DOI: 10.1002/ajh.2830040402. View

14.

Cines D, Schreiber A . Immune thrombocytopenia. Use of a Coombs antiglobulin test to detect IgG and C3 on platelets. N Engl J Med. 1979; 300(3):106-11. DOI: 10.1056/NEJM197901183000302. View

15.

McGrath K, Stuart J, Richards 2nd F . Correlation between serum IgG, platelet membrane IgG, and platelet function in hypergammaglobulinaemic states. Br J Haematol. 1979; 42(4):585-91. DOI: 10.1111/j.1365-2141.1979.tb01171.x. View

16.

Leporrier M, Dighiero G, Auzemery M, Binet J . Detection and quantification of platelet-bound antibodies with immunoperoxidase. Br J Haematol. 1979; 42(4):605-11. DOI: 10.1111/j.1365-2141.1979.tb01173.x. View

17.

Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979; 76(9):4350-4. PMC: 411572. DOI: 10.1073/pnas.76.9.4350. View

18.

Weiss H, Witte L, Kaplan K, Lages B, Chernoff A, Nossel H . Heterogeneity in storage pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in alpha-granules, platelet factor 4, beta-thromboglobulin, and platelet-derived growth factor. Blood. 1979; 54(6):1296-319. View

19.

Shuman M, Levine S . Relationship between secretion of platelet Factor 4 and thrombin generation during in vitro blood clotting. J Clin Invest. 1980; 65(2):307-13. PMC: 371368. DOI: 10.1172/JCI109673. View

20.

Kernoff L, Blake K, Shackleton D . Influence of the amount of platelet-bound IgG on platelet survival and site of sequestration in autoimmune thrombocytopenia. Blood. 1980; 55(5):730-3. View