Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1991 Dec;139(6):1471–1484.

Heterogeneous distribution of Weibel-Palade bodies and von Willebrand factor along the porcine vascular tree.

J Gebrane-Younès 1, L Drouet 1, J P Caen 1, L Orcel 1
PMCID: PMC1886451  PMID: 1750513

Abstract

Vessels obtained from different levels of pig vascular tree were examined by transmission electron microscope, with the aim of determining whether or not their endothelial cells contain Weibel-Palade bodies (WPB). As these organelles are known to store the von Willebrand factor (vWF), a two-step immunogold labeling of this protein also was performed. Our results showed for the first time a heterogeneous distribution of WPB along the vascular tree of the normal pig: These structures were absent from the thoracic aorta, rare in the abdominal aorta, present in myocardial capillaries, and numerous in the inferior vena cava and pulmonary artery. Atypical WPB devoid of tubules were seen in all endothelial cells. The ultrastructural labeling of vWF demonstrated its presence only in the WPB, being absent in the subendothelium, and showed the same variation in its distribution along the vascular tree as for its storage organelle. Pigs homozygous for the von Willebrand disease were found to have only the atypical WPB, and do not express the vWF.

Full text

PDF
1471

Images in this article

1474Figure 1
on p.1474
1474p1474-b
on p.1474
1474Figure 2
on p.1474
1474p1474-d
on p.1474
1475Figure 3
on p.1475
1476Figure 4
on p.1476
1477Figure 5
on p.1477
1477Figure 6
on p.1477
1478Figure 7
on p.1478
1478Figure 8
on p.1478
1479Figure 9
on p.1479
1479Figure 10 11
on p.1479
1480Figure 12
on p.1480
1480Figure 13
on p.1480

Selected References

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

  1. Armbruster B. L., Carlemalm E., Chiovetti R., Garavito R. M., Hobot J. A., Kellenberger E., Villiger W. Specimen preparation for electron microscopy using low temperature embedding resins. J Microsc. 1982 Apr;126(Pt 1):77–85. doi: 10.1111/j.1365-2818.1982.tb00358.x. [DOI] [PubMed] [Google Scholar]
  2. Bahnak B. R., Wu Q. Y., Coulombel L., Assouline Z., Kerbiriou-Nabias D., Piétu G., Drouet L., Caen J. P., Meyer D. Expression of von Willebrand factor in porcine vessels: heterogeneity at the level of von Willebrand factor mRNA. J Cell Physiol. 1989 Feb;138(2):305–310. doi: 10.1002/jcp.1041380212. [DOI] [PubMed] [Google Scholar]
  3. Bowie E. J., Fass D. N., Owen C. A., Jr Hemostatic effect of transfused Willebrand factor in porcine von Willebrand's disease. Similarities to the human disease. Haemostasis. 1980;9(6):352–365. doi: 10.1159/000214377. [DOI] [PubMed] [Google Scholar]
  4. Castillo R., Escolar G., Monteagudo J., Ordinas A., Garrido M., Moia M., Federici A. B., Mannucci P. M. Role for platelet von Willebrand factor in supporting platelet-vessel wall interactions in von Willebrand disease. Am J Hematol. 1989 Jul;31(3):153–158. doi: 10.1002/ajh.2830310303. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Fass D. N., Brockway W. J., Owen C. A., Jr, Bowie E. J. Factor VIII (Willebrand) antigen and ristocetin-Willebrand factor in pigs with von Willebrand's disease. Thromb Res. 1976 Mar;8(3):319–327. doi: 10.1016/0049-3848(76)90025-6. [DOI] [PubMed] [Google Scholar]
  7. Fressinaud E., Baruch D., Rothschild C., Baumgartner H. R., Meyer D. Platelet von Willebrand factor: evidence for its involvement in platelet adhesion to collagen. Blood. 1987 Oct;70(4):1214–1217. [PubMed] [Google Scholar]
  8. Fuchs A., Weibel E. R. Morphometrische Untersuchung der Verteilung einer spezifischen cytoplasmatischen Organelle in Endothelzellen der Ratte. Z Zellforsch Mikrosk Anat. 1966;73(1):1–9. [PubMed] [Google Scholar]
  9. Fuster V., Fass D. N., Kaye M. P., Josa M., Zinsmeister A. R., Bowie E. J. Arteriosclerosis in normal and von Willebrand pigs: long-term prospective study and aortic transplantation study. Circ Res. 1982 Nov;51(5):587–593. doi: 10.1161/01.res.51.5.587. [DOI] [PubMed] [Google Scholar]
  10. Fuster W., Bowie E. J., Lewis J. C., Fass D. N., Owen C. A., Jr, Brown A. L. Resistance to arteriosclerosis in pigs with von Willebrand's disease. Spontaneous and high cholesterol diet-induced arteriosclerosis. J Clin Invest. 1978 Mar;61(3):722–730. doi: 10.1172/JCI108985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gebrane-Younes J., Hoang N. M., Orcel L. Ultrastructure of human umbilical vessels: a possible role in amniotic fluid formation? Placenta. 1986 Mar-Apr;7(2):173–185. doi: 10.1016/s0143-4004(86)80008-x. [DOI] [PubMed] [Google Scholar]
  12. Gebrane J., Orcel L. The evolution of experimental endarteritis in the rabbit abdominal aorta. Light and transmission electron microscopy. Virchows Arch A Pathol Anat Histopathol. 1982;398(2):205–220. doi: 10.1007/BF00618870. [DOI] [PubMed] [Google Scholar]
  13. Gerrity R. G., Cliff W. J. The aortic tunica intima in young and aging rats. Exp Mol Pathol. 1972 Jun;16(3):382–402. doi: 10.1016/0014-4800(72)90012-3. [DOI] [PubMed] [Google Scholar]
  14. Griggs T. R., Webster W. P., Cooper H. A., Wagner R. H., Brinkhous K. M. Von Willebrand factor: gene dosage relationships and transfusion response in bleeder swine--a new bioassay. Proc Natl Acad Sci U S A. 1974 May;71(5):2087–2090. doi: 10.1073/pnas.71.5.2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Jeanneau C., Sultan Y. Localization of factor VIII/von Willebrand factor antigen by immunoelectron microscopy in human endothelial cells using Fab fragments coupled to peroxidase. J Histochem Cytochem. 1982 Nov;30(11):1091–1096. doi: 10.1177/30.11.6815260. [DOI] [PubMed] [Google Scholar]
  17. Levine J. D., Harlan J. M., Harker L. A., Joseph M. L., Counts R. B. Thrombin-mediated release of factor VIII antigen from human umbilical vein endothelial cells in culture. Blood. 1982 Aug;60(2):531–534. [PubMed] [Google Scholar]
  18. Loesberg C., Gonsalves M. D., Zandbergen J., Willems C., van Aken W. G., Stel H. V., Van Mourik J. A., De Groot P. G. The effect of calcium on the secretion of factor VIII-related antigen by cultured human endothelial cells. Biochim Biophys Acta. 1983 Sep 22;763(2):160–168. doi: 10.1016/0167-4889(83)90039-3. [DOI] [PubMed] [Google Scholar]
  19. Meyer D., Obert B., Pietu G., Lavergne J. M., Zimmerman T. S. Multimeric structure of factor VIII/von Willebrand factor in von Willebrand's disease. J Lab Clin Med. 1980 Apr;95(4):590–602. [PubMed] [Google Scholar]
  20. Monahan-Earley R. A., Isomura T., Garcia R. I., Galli S. J., Dvorak H. F., Dvorak A. M. Nonspecific esterase activity expressed in Weibel-Palade bodies of cloned guinea pig aortic endothelial cells. J Histochem Cytochem. 1987 May;35(5):531–539. doi: 10.1177/35.5.3559181. [DOI] [PubMed] [Google Scholar]
  21. Mukai K., Rosai J., Burgdorf W. H. Localization of factor VIII-related antigen in vascular endothelial cells using an immunoperoxidase method. Am J Surg Pathol. 1980 Jun;4(3):273–276. doi: 10.1097/00000478-198006000-00008. [DOI] [PubMed] [Google Scholar]
  22. Nadji M., Morales A. R., Ziegles-Weissman J., Penneys N. S. Kaposi's sarcoma: immunohistologic evidence for an endothelial origin. Arch Pathol Lab Med. 1981 May;105(5):274–275. [PubMed] [Google Scholar]
  23. Ohmori K., Fretto L. J., Harrison R. L., Switzer M. E., Erickson H. P., McKee P. A. Electron microscopy of human factor VIII/Von Willebrand glycoprotein: effect of reducing reagents on structure and function. J Cell Biol. 1982 Nov;95(2 Pt 1):632–640. doi: 10.1083/jcb.95.2.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pieraggi M. T., Bouissou H. Aorte Humaine: endothélium et athérome. Ann Pathol. 1981;1(4):271–279. [PubMed] [Google Scholar]
  25. Rand J. H., Badimon L., Gordon R. E., Uson R. R., Fuster V. Distribution of von Willebrand factor in porcine intima varies with blood vessel type and location. Arteriosclerosis. 1987 May-Jun;7(3):287–291. doi: 10.1161/01.atv.7.3.287. [DOI] [PubMed] [Google Scholar]
  26. Rand J. H., Gordon R. E., Sussman I. I., Chu S. V., Solomon V. Electron microscopic localization of factor-VIII-related antigen in adult human blood vessels. Blood. 1982 Sep;60(3):627–634. [PubMed] [Google Scholar]
  27. Rand J. H., Sussman I. I., Gordon R. E., Chu S. V., Solomon V. Localization of factor-VIII-related antigen in human vascular subendothelium. Blood. 1980 May;55(5):752–756. [PubMed] [Google Scholar]
  28. Reidy M. A., Chopek M., Chao S., McDonald T., Schwartz S. M. Injury induces increase of von Willebrand factor in rat endothelial cells. Am J Pathol. 1989 Apr;134(4):857–864. [PMC free article] [PubMed] [Google Scholar]
  29. Reinders J. H., De Groot P. G., Gonsalves M. D., Zandbergen J., Loesberg C., Van Mourik J. A. Isolation of a storage and secretory organelle containing Von Willebrand protein from cultured human endothelial cells. Biochim Biophys Acta. 1984 Jul 20;804(3):361–369. doi: 10.1016/0167-4889(84)90140-x. [DOI] [PubMed] [Google Scholar]
  30. Reinders J. H., de Groot P. G., Sixma J. J., van Mourik J. A. Storage and secretion of von Willebrand factor by endothelial cells. Haemostasis. 1988;18(4-6):246–261. doi: 10.1159/000215811. [DOI] [PubMed] [Google Scholar]
  31. Ribes J. A., Francis C. W., Wagner D. D. Fibrin induces release of von Willebrand factor from endothelial cells. J Clin Invest. 1987 Jan;79(1):117–123. doi: 10.1172/JCI112771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Roth J., Bendayan M., Carlemalm E., Villiger W., Garavito M. Enhancement of structural preservation and immunocytochemical staining in low temperature embedded pancreatic tissue. J Histochem Cytochem. 1981 May;29(5):663–671. doi: 10.1177/29.5.6166664. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Slayter H., Loscalzo J., Bockenstedt P., Handin R. I. Native conformation of human von Willebrand protein. Analysis by electron microscopy and quasi-elastic light scattering. J Biol Chem. 1985 Jul 15;260(14):8559–8563. [PubMed] [Google Scholar]
  35. Sporn L. A., Marder V. J., Wagner D. D. Differing polarity of the constitutive and regulated secretory pathways for von Willebrand factor in endothelial cells. J Cell Biol. 1989 Apr;108(4):1283–1289. doi: 10.1083/jcb.108.4.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Sporn L. A., Marder V. J., Wagner D. D. von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively. Blood. 1987 May;69(5):1531–1534. [PubMed] [Google Scholar]
  38. Steinsiepe K. F., Weibel E. R. Elektronenmikroskopische Untersuchungen an spezifischen Organellen von Endothelzellen des Frosches (Rana temporaria) Z Zellforsch Mikrosk Anat. 1970;108(1):105–126. [PubMed] [Google Scholar]
  39. Sussman I. I., Rand J. H. Subendothelial deposition of von Willebrand's factor requires the presence of endothelial cells. J Lab Clin Med. 1982 Oct;100(4):526–532. [PubMed] [Google Scholar]
  40. Tannenbaum S. H., Rick M. E., Shafer B., Gralnick H. R. Subendothelial matrix of cultured endothelial cells contains fully processed high molecular weight von Willebrand factor. J Lab Clin Med. 1989 Mar;113(3):372–378. [PubMed] [Google Scholar]
  41. Tschopp T. B., Weiss H. J., Baumgartner H. R. Decreased adhesion of platelets to subendothelium in von Willebrand's disease. J Lab Clin Med. 1974 Feb;83(2):296–300. [PubMed] [Google Scholar]
  42. Verweij C. L. Biosynthesis of human von Willebrand factor. Haemostasis. 1988;18(4-6):224–245. doi: 10.1159/000215810. [DOI] [PubMed] [Google Scholar]
  43. WEIBEL E. R., PALADE G. E. NEW CYTOPLASMIC COMPONENTS IN ARTERIAL ENDOTHELIA. J Cell Biol. 1964 Oct;23:101–112. doi: 10.1083/jcb.23.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wagner D. D., Fay P. J., Sporn L. A., Sinha S., Lawrence S. O., Marder V. J. Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1955–1959. doi: 10.1073/pnas.84.7.1955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wagner D. D., Marder V. J. Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol. 1984 Dec;99(6):2123–2130. doi: 10.1083/jcb.99.6.2123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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]
  47. Warhol M. J., Sweet J. M. The ultrastructural localization of von Willebrand factor in endothelial cells. Am J Pathol. 1984 Nov;117(2):310–315. [PMC free article] [PubMed] [Google Scholar]
  48. Wu Q. Y., Bahnak B. R., Coulombel L., Kerbiriou-Nabias D., Drouet L., Piétu G., Meulien P., Pavirani A., Caen J. P., Meyer D. Analysis of von Willebrand factor mRNA from the lung of pigs with severe von Willebrand disease by using a human cDNA probe. Blood. 1988 May;71(5):1341–1346. [PubMed] [Google Scholar]
  49. Wu Q. Y., Drouet L., Carrier J. L., Rothschild C., Berard M., Rouault C., Caen J. P., Meyer D. Differential distribution of von Willebrand factor in endothelial cells. Comparison between normal pigs and pigs with von Willebrand disease. Arteriosclerosis. 1987 Jan-Feb;7(1):47–54. doi: 10.1161/01.atv.7.1.47. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES