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. 1969 Sep;48(9):1615–1626. doi: 10.1172/JCI106127

Measurement of thrombopoiesis in rabbits using 75selenomethionine

Bruce L Evatt 1, Jack Levin 1
PMCID: PMC535733  PMID: 5822574

Abstract

Incorporation of 75selenomethionine (75SeM) has been used to study platelet production in rabbits. Radioactivity of platelets was low after the intravenous administration of 75SeM and rose to a maximum approximately 3 days after administration. Platelet radioactivity was independent of concurrent plasma levels. The life span of rabbit platelets, as estimated with this technique, was 4-5 days. In vivo reutilization of 75SeM previously incorporated into plasma proteins was not detected. In vitro incorporation of 75SeM by platelets in platelet-rich plasma was not demonstrated.

Acute hemorrhage 24 hr before administration of 75SeM increased the incorporation of 75SeM into platelets. Transfusion-induced thrombocytosis reduced the incorporation of 75SeM to approximately 30% of that observed in control animals. Suppression of bone marrow function with nitrogen mustard resulted in decreased numbers of platelets in the circulation, and a decrease in incorporation of 75SeM. Delayed appearance of 75SeM was observed in circulating platelets during recovery from marrow suppression. Injection of 75-225 ml of plasma from thrombocytopenic donors into normal rabbits increased incorporation of 75SeM into platelets while normal plasma did not have this effect.

The rate of appearance of 75SeM in circulating platelets appears to provide a sensitive and specific method for the study of production of platelets by megakaryocytes. The data suggest more rapid entry of platelets into the circulation, and a sustained increase in incorporation of 75SeM into platelet protein after stimulation of platelet production. The results are consistent with the concept of a humoral agent (thrombopoietin) that acts on megakaryocytes to regulate platelet production.

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Selected References

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

  1. Abildgaard C. F., Simone J. V. Thrombopoiesis. Semin Hematol. 1967 Oct;4(4):424–452. [PubMed] [Google Scholar]
  2. Awwad H. K., Adelstein S. J., Potchen E. J., Dealy J. B., Jr The interconversion and reutilization of injected 75-Se-selenomethionine in the rat. J Biol Chem. 1967 Feb 10;242(3):492–500. [PubMed] [Google Scholar]
  3. Awwad H. K., Potchen E. J., Adelstein S. J., Dealy J. B., Jr The regional distribution of Se75-selenomethionine in the rat. Metabolism. 1966 Apr;15(4):370–378. doi: 10.1016/0026-0495(66)90151-x. [DOI] [PubMed] [Google Scholar]
  4. Booyse F., Rafelson M. E., Jr In vitro incorporation of amino-acids into the contractile protein of human blood platelets. Nature. 1967 Jul 15;215(5098):283–284. doi: 10.1038/215283a0. [DOI] [PubMed] [Google Scholar]
  5. Bull B. S., Schneiderman M. A., Brecher G. Platelet counts with the Coulter counter. Am J Clin Pathol. 1965 Dec;44(6):678–688. doi: 10.1093/ajcp/44.6.678. [DOI] [PubMed] [Google Scholar]
  6. COONEY D. P., SMITH B. A. MATURATION TIME OF RABBIT MEGAKARYOCYTES. Br J Haematol. 1965 Jul;11:484–487. doi: 10.1111/j.1365-2141.1965.tb06612.x. [DOI] [PubMed] [Google Scholar]
  7. CRADDOCK C. G., Jr, ADAMS W. S., PERRY S., LAWRENCE J. S. The dynamics of platelet production as studied by a depletion technique in normal and irradiated dogs. J Lab Clin Med. 1955 Jun;45(6):906–919. [PubMed] [Google Scholar]
  8. De Gabriele G., Penington D. G. Physiology of the regulation of platelet production. Br J Haematol. 1967 Mar;13(2):202–209. doi: 10.1111/j.1365-2141.1967.tb08732.x. [DOI] [PubMed] [Google Scholar]
  9. De Gabriele G., Penington D. G. Regulation of platelet production: "thrombopoietin". Br J Haematol. 1967 Mar;13(2):210–215. doi: 10.1111/j.1365-2141.1967.tb08733.x. [DOI] [PubMed] [Google Scholar]
  10. EBBE S., STOHLMAN F., Jr MEGAKARYOCYTOPOIESIS IN THE RAT. Blood. 1965 Jul;26:20–35. [PubMed] [Google Scholar]
  11. ERSLEV A. Humoral regulation of red cell production. Blood. 1953 Apr;8(4):349–357. [PubMed] [Google Scholar]
  12. Ebbe S., Stohlman F., Jr, Donovan J., Howard D. Platelet survival in rats with transfusion-induced thrombocytosis. J Lab Clin Med. 1966 Nov;68(5):813–823. [PubMed] [Google Scholar]
  13. Ebbe S., Stohlman F., Jr, Overcash J., Donovan J., Howard D. Megakaryocyte size in thrombocytopenic and normal rats. Blood. 1968 Sep;32(3):383–392. [PubMed] [Google Scholar]
  14. HANSSON E., BLAU M. INCORPORATION OF SE75-SELENOMETHIONINE INTO PANCREATIC JUICE PROTEINS IN VIVO. Biochem Biophys Res Commun. 1963 Sep 10;13:71–74. doi: 10.1016/0006-291x(63)90165-7. [DOI] [PubMed] [Google Scholar]
  15. Hansson E., Jacobsson S. O. Uptake of [75Se] selenomethionine in the tissues of the mouse studied by whole-body autoradiography. Biochim Biophys Acta. 1966 Feb 28;115(2):285–293. doi: 10.1016/0304-4165(66)90427-2. [DOI] [PubMed] [Google Scholar]
  16. Harker L. A. Kinetics of thrombopoiesis. J Clin Invest. 1968 Mar;47(3):458–465. doi: 10.1172/JCI105742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KELEMEN E., LEHOCZKY D., CSERHATI I., KRIZSA F., RAK K. Demonstrability of a serum factor inducing thrombocytosis prior to acute rises of platelets in mice and men. Acta Haematol. 1963;29:16–26. doi: 10.1159/000207321. [DOI] [PubMed] [Google Scholar]
  18. KINSELL L. W., MARGEN S. Studies in methionine metabolism; the fate of intravenously administered S35-labeled-methionine in normal adult males, in patients with chronic hepatic disease, idiopathic hypoproteinemia and Cushing's syndrome. J Clin Invest. 1950 Feb;29(2):238–250. doi: 10.1172/JCI102251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MCCONNELL K. P., CHO G. J. TRANSMUCOSAL MOVEMENT OF SELENIUM. Am J Physiol. 1965 Jun;208:1191–1195. doi: 10.1152/ajplegacy.1965.208.6.1191. [DOI] [PubMed] [Google Scholar]
  20. MCDONALD T. P., ODELL T. T., Jr, GOSSLEE D. G. PLATELET SIZE IN RELATION TO PLATELET AGE. Proc Soc Exp Biol Med. 1964 Mar;115:684–689. doi: 10.3181/00379727-115-29006. [DOI] [PubMed] [Google Scholar]
  21. McClure P. D., Choi S. I. Thrombopoietin and erythropoietin levels in idiopathic thrombocytopenic purpura and iron-deficiency anaemia. Br J Haematol. 1968 Oct;15(4):351–354. doi: 10.1111/j.1365-2141.1968.tb01549.x. [DOI] [PubMed] [Google Scholar]
  22. ODELL T. T., Jr, MCDONALD T. P., HOWSDEN F. L. NATIVE AND FOREIGN STIMULATORS OF PLATELET PRODUCTION. J Lab Clin Med. 1964 Sep;64:418–424. [PubMed] [Google Scholar]
  23. ODELL T. T., Jr, MCDONALD T. P. TWO MECHANISMS OF SULFATE-S35 UPTAKE BY BLOOD PLATELETS OF RATS. Am J Physiol. 1964 Mar;206:580–584. doi: 10.1152/ajplegacy.1964.206.3.580. [DOI] [PubMed] [Google Scholar]
  24. ODELL T. T., Jr, McDONALD T. P., ASANO M. Response of rat megakaryocytes and platelets to bleeding. Acta Haematol. 1962;27:171–179. doi: 10.1159/000206778. [DOI] [PubMed] [Google Scholar]
  25. ODELL T. T., Jr, McDONALD T. P., DETWILER T. C. Stimulation of platelet production by serum of platelet-depleted rats. Proc Soc Exp Biol Med. 1961 Nov;108:428–431. doi: 10.3181/00379727-108-26958. [DOI] [PubMed] [Google Scholar]
  26. ODELL T. T., Jr, TAUSCHE F. G., FURTH J. Platelet life span as measured by transfusion of isotopically labeled platelets into rats. Acta Haematol. 1955 Jan;13(1):45–52. doi: 10.1159/000204921. [DOI] [PubMed] [Google Scholar]
  27. Odell T. T., Jr, Jackson C. W., Reiter R. S. Depression of the megakaryocyte-platelet system in rats by transfusion of platelets. Acta Haematol. 1967;38(1):34–42. doi: 10.1159/000208997. [DOI] [PubMed] [Google Scholar]
  28. Penington D. G. Studies of platelet production and sequestration in the experimental animal. Proc R Soc Med. 1968 Jun;61(6):601–603. [PMC free article] [PubMed] [Google Scholar]
  29. Penner J. A. Investigation of erythrocyte turnover with selenium-75-labeled methionine. J Lab Clin Med. 1966 Mar;67(3):427–438. [PubMed] [Google Scholar]
  30. Qawwad H. K., Potchen E. J., Adelstein S. J., Dealy J. B., Jr Se75-selenomethionine incorporation into human plasma proteins and erythrocytes. Metabolism. 1966 Jul;15(7):626–640. doi: 10.1016/0026-0495(66)90124-7. [DOI] [PubMed] [Google Scholar]
  31. SCHULMAN I., PIERCE M., LUKENS A., CURRIMBHOY Z. Studies on thrombopoiesis. I. A factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its deficiency. Blood. 1960 Jul;16:943–957. [PubMed] [Google Scholar]
  32. SPECTOR B. In vivo transfer of a thrombopoietic factor. Proc Soc Exp Biol Med. 1961 Oct;108:146–149. doi: 10.3181/00379727-108-26874. [DOI] [PubMed] [Google Scholar]
  33. SPENCER R. P., BLAU M. Intestinal transport of selenium-75 selenomethionine. Science. 1962 Apr 13;136(3511):155–156. doi: 10.1126/science.136.3511.155. [DOI] [PubMed] [Google Scholar]
  34. STRUMIA M. M., SAMPLE A. B., HART E. D. An improved micro hematocrit method. Am J Clin Pathol. 1954 Sep;24(9):1016–1024. doi: 10.1093/ajcp/24.9.1016. [DOI] [PubMed] [Google Scholar]
  35. Warshaw A. L., Laster L., Shulman N. R. Protein synthesis by human platelets. J Biol Chem. 1967 May 10;242(9):2094–2097. [PubMed] [Google Scholar]

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