Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Dec;92(6):3023–3028. doi: 10.1172/JCI116926

Gray platelet syndrome. Dissociation between abnormal sorting in megakaryocyte alpha-granules and normal sorting in Weibel-Palade bodies of endothelial cells.

J Gebrane-Younès 1, E M Cramer 1, L Orcel 1, J P Caen 1
PMCID: PMC288507  PMID: 7504696

Abstract

The gray platelet syndrome (GPS) is a rare congenital bleeding disorder in which megakaryocytes and platelets are deficient in alpha-granule secretory proteins. Since the Weibel-Palade bodies (WPB) of endothelial cells as well as the alpha-granules contain the von Willebrand Factor (vWF) and P-selectin, we examined by transmission electron microscopy the dermis capillary network of two patients with GPS. Endothelial cells showed the presence of normal WPB with typical internal tubules. Using single and double immunogold labeling for vWF and P-selectin, we detected vWF within WPB, where it was codistributed with the tubules, whereas P-selectin delineated the outline of WPB. Therefore, the fundamental targeting defect in GPS is specific to the megakaryocytic cell line.

Full text

PDF
3025

Images in this article

3024Image
on p.3024
3024Image
on p.3024
3024Image
on p.3024
3025Image
on p.3025
3026Image
on p.3026

Selected References

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

  1. Berman C. L., Yeo E. L., Wencel-Drake J. D., Furie B. C., Ginsberg M. H., Furie B. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein. J Clin Invest. 1986 Jul;78(1):130–137. doi: 10.1172/JCI112542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berndt M. C., Castaldi P. A., Gordon S., Halley H., McPherson V. J. Morphological and biochemical confirmation of gray platelet syndrome in two siblings. Aust N Z J Med. 1983 Aug;13(4):387–390. doi: 10.1111/j.1445-5994.1983.tb04488.x. [DOI] [PubMed] [Google Scholar]
  3. Bonfanti R., Furie B. C., Furie B., Wagner D. D. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1989 Apr;73(5):1109–1112. [PubMed] [Google Scholar]
  4. Breton-Gorius J., Vainchenker W., Nurden A., Levy-Toledano S., Caen J. Defective alpha-granule production in megakaryocytes from gray platelet syndrome: ultrastructural studies of bone marrow cells and megakaryocytes growing in culture from blood precursors. Am J Pathol. 1981 Jan;102(1):10–19. [PMC free article] [PubMed] [Google Scholar]
  5. Cramer E. M., Meyer D., le Menn R., Breton-Gorius J. Eccentric localization of von Willebrand factor in an internal structure of platelet alpha-granule resembling that of Weibel-Palade bodies. Blood. 1985 Sep;66(3):710–713. [PubMed] [Google Scholar]
  6. Cramer E. M., Savidge G. F., Vainchenker W., Berndt M. C., Pidard D., Caen J. P., Massé J. M., Breton-Gorius J. Alpha-granule pool of glycoprotein IIb-IIIa in normal and pathologic platelets and megakaryocytes. Blood. 1990 Mar 15;75(6):1220–1227. [PubMed] [Google Scholar]
  7. Cramer E. M., Vainchenker W., Vinci G., Guichard J., Breton-Gorius J. Gray platelet syndrome: immunoelectron microscopic localization of fibrinogen and von Willebrand factor in platelets and megakaryocytes. Blood. 1985 Dec;66(6):1309–1316. [PubMed] [Google Scholar]
  8. Disdier M., Morrissey J. H., Fugate R. D., Bainton D. F., McEver R. P. Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway. Mol Biol Cell. 1992 Mar;3(3):309–321. doi: 10.1091/mbc.3.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ewenstein B. M., Warhol M. J., Handin R. I., Pober J. S. Composition of the von Willebrand factor storage organelle (Weibel-Palade body) isolated from cultured human umbilical vein endothelial cells. J Cell Biol. 1987 May;104(5):1423–1433. doi: 10.1083/jcb.104.5.1423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gebrane-Younès J., Drouet L., Caen J. P., Orcel L. Heterogeneous distribution of Weibel-Palade bodies and von Willebrand factor along the porcine vascular tree. Am J Pathol. 1991 Dec;139(6):1471–1484. [PMC free article] [PubMed] [Google Scholar]
  11. Geng J. G., Bevilacqua M. P., Moore K. L., McIntyre T. M., Prescott S. M., Kim J. M., Bliss G. A., Zimmerman G. A., McEver R. P. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990 Feb 22;343(6260):757–760. doi: 10.1038/343757a0. [DOI] [PubMed] [Google Scholar]
  12. Gerrard J. M., Phillips D. R., Rao G. H., Plow E. F., Walz D. A., Ross R., Harker L. A., White J. G. Biochemical studies of two patients with the gray platelet syndrome. Selective deficiency of platelet alpha granules. J Clin Invest. 1980 Jul;66(1):102–109. doi: 10.1172/JCI109823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Han Z. C., Caen J. P. Are megakaryocytes and endothelial cells sisters? J Lab Clin Med. 1993 Jun;121(6):821–825. [PubMed] [Google Scholar]
  14. Harrison P., Cramer E. M. Platelet alpha-granules. Blood Rev. 1993 Mar;7(1):52–62. doi: 10.1016/0268-960x(93)90024-x. [DOI] [PubMed] [Google Scholar]
  15. Harrison P., Wilbourn B., Debili N., Vainchenker W., Breton-Gorius J., Lawrie A. S., Masse J. M., Savidge G. F., Cramer E. M. Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets. J Clin Invest. 1989 Oct;84(4):1320–1324. doi: 10.1172/JCI114300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jaffe E. A., Hoyer L. W., Nachman R. L. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest. 1973 Nov;52(11):2757–2764. doi: 10.1172/JCI107471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johnston G. I., Cook R. G., McEver R. P. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989 Mar 24;56(6):1033–1044. doi: 10.1016/0092-8674(89)90636-3. [DOI] [PubMed] [Google Scholar]
  18. Köhler M., Hellstern P., Morgenstern E., Mueller-Eckhardt C., Berberich R., Meiser R. J., Scheffler P., Wenzel E. Gray platelet syndrome: selective alpha-granule deficiency and thrombocytopenia due to increased platelet turnover. Blut. 1985 Jun;50(6):331–340. doi: 10.1007/BF00320926. [DOI] [PubMed] [Google Scholar]
  19. Levy-Toledano S., Caen J. P., Breton-Gorius J., Rendu F., Cywiner-Golenzer C., Dupuy E., Legrand Y., Maclouf J. Gray platelet syndrome: alpha-granule deficiency. Its influence on platelet function. J Lab Clin Med. 1981 Dec;98(6):831–848. [PubMed] [Google Scholar]
  20. May G. L., Dunlop L. C., Sztelma K., Berndt M. C., Sorrell T. C. GMP-140 (P-selectin) inhibits human neutrophil activation by lipopolysaccharide: analysis by proton magnetic resonance spectroscopy. Biochem Biophys Res Commun. 1992 Mar 31;183(3):1062–1069. doi: 10.1016/s0006-291x(05)80298-0. [DOI] [PubMed] [Google Scholar]
  21. McEver R. P., Beckstead J. H., Moore K. L., Marshall-Carlson L., Bainton D. F. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest. 1989 Jul;84(1):92–99. doi: 10.1172/JCI114175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McEver R. P., Martin M. N. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem. 1984 Aug 10;259(15):9799–9804. [PubMed] [Google Scholar]
  23. Nachman R., Levine R., Jaffe E. A. Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. J Clin Invest. 1977 Oct;60(4):914–921. doi: 10.1172/JCI108846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nurden A. T., Kunicki T. J., Dupuis D., Soria C., Caen J. P. Specific protein and glycoprotein deficiencies in platelets isolated from two patients with the gray platelet syndrome. Blood. 1982 Apr;59(4):709–718. [PubMed] [Google Scholar]
  25. Reinders J. H., de Groot P. G., Dawes J., Hunter N. R., van Heugten H. A., Zandbergen J., Gonsalves M. D., van Mourik J. A. Comparison of secretion and subcellular localization of von Willebrand protein with that of thrombospondin and fibronectin in cultured human vascular endothelial cells. Biochim Biophys Acta. 1985 Mar 21;844(3):306–313. doi: 10.1016/0167-4889(85)90131-4. [DOI] [PubMed] [Google Scholar]
  26. Rindler M. J. Biogenesis of storage granules and vesicles. Curr Opin Cell Biol. 1992 Aug;4(4):616–622. doi: 10.1016/0955-0674(92)90080-v. [DOI] [PubMed] [Google Scholar]
  27. Rosa J. P., George J. N., Bainton D. F., Nurden A. T., Caen J. P., McEver R. P. Gray platelet syndrome. Demonstration of alpha granule membranes that can fuse with the cell surface. J Clin Invest. 1987 Oct;80(4):1138–1146. doi: 10.1172/JCI113171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roth J. Applications of immunocolloids in light microscopy. Preparation of protein A-silver and protein A-gold complexes and their application for localization of single and multiple antigens in paraffin sections. J Histochem Cytochem. 1982 Jul;30(7):691–696. doi: 10.1177/30.7.7050239. [DOI] [PubMed] [Google Scholar]
  29. Sengel A., Stoebner P. Golgi origin of tubular inclusions in endothelial cells. J Cell Biol. 1970 Jan;44(1):223–226. doi: 10.1083/jcb.44.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sporn L. A., Chavin S. I., Marder V. J., Wagner D. D. Biosynthesis of von Willebrand protein by human megakaryocytes. J Clin Invest. 1985 Sep;76(3):1102–1106. doi: 10.1172/JCI112064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sporn L. A., Marder V. J., Wagner D. D. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell. 1986 Jul 18;46(2):185–190. doi: 10.1016/0092-8674(86)90735-x. [DOI] [PubMed] [Google Scholar]
  32. Stenberg P. E., McEver R. P., Shuman M. A., Jacques Y. V., Bainton D. F. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol. 1985 Sep;101(3):880–886. doi: 10.1083/jcb.101.3.880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tuddenham E. G., Lazarchick J., Hoyer L. W. Synthesis and release of factor VIII by cultured human endothelial cells. Br J Haematol. 1981 Apr;47(4):617–626. doi: 10.1111/j.1365-2141.1981.tb02691.x. [DOI] [PubMed] [Google Scholar]
  34. Vinci G., Tabilio A., Deschamps J. F., Van Haeke D., Henri A., Guichard J., Tetteroo P., Lansdorp P. M., Hercend T., Vainchenker W. Immunological study of in vitro maturation of human megakaryocytes. Br J Haematol. 1984 Apr;56(4):589–605. doi: 10.1111/j.1365-2141.1984.tb02184.x. [DOI] [PubMed] [Google Scholar]
  35. Wagner D. D., Olmsted J. B., Marder V. J. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol. 1982 Oct;95(1):355–360. doi: 10.1083/jcb.95.1.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wagner D. D., Saffaripour S., Bonfanti R., Sadler J. E., Cramer E. M., Chapman B., Mayadas T. N. Induction of specific storage organelles by von Willebrand factor propolypeptide. Cell. 1991 Jan 25;64(2):403–413. doi: 10.1016/0092-8674(91)90648-i. [DOI] [PubMed] [Google Scholar]
  37. White J. G. Ultrastructural studies of the gray platelet syndrome. Am J Pathol. 1979 May;95(2):445–462. [PMC free article] [PubMed] [Google Scholar]
  38. Wong C. S., Gamble J. R., Skinner M. P., Lucas C. M., Berndt M. C., Vadas M. A. Adhesion protein GMP140 inhibits superoxide anion release by human neutrophils. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2397–2401. doi: 10.1073/pnas.88.6.2397. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES