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. 1995 Jun;146(6):1397–1405.

Histogenesis and ultrastructure of pancreatic islet graft microvasculature. Evidence for graft revascularization by endothelial cells of host origin.

P Vajkoczy 1, A M Olofsson 1, H A Lehr 1, R Leiderer 1, F Hammersen 1, K E Arfors 1, M D Menger 1
PMCID: PMC1870898  PMID: 7539980

Abstract

In previous studies we have demonstrated that syngeneic and xenogeneic pancreatic islet grafts are revascularized within a 10 to 14-day period after transplantation. With the combined use of intravital and electron microscopy, as well as immunohistochemistry using a set of species-specific or -crossreacting antibodies to endothelial cell antigens, we investigated 1) the origin of the endothelium of the newly formed capillaries in free pancreatic islet isografts (hamster-->hamster) and xenografts (rat-->hamster), and 2) the ultrastructural characteristics of these microvessels. Intravital microscopy demonstrated that newly formed microvessels grow from the vascular bed of the host muscle tissue into the islet grafts. Immunohistochemical analysis of host tissue and transplanted islets with antibodies against factor VIII (recognizing both hamster and rat factor VIII), bovine PECAM-1 (CD31; endoCAM, crossreacting with hamster but not rat PECAM-1), and rat ICAM-1 (CD54, non-crossreacting with hamster ICAM-1) showed that the transplanted rat islets were revascularized by endothelium of hamster (host) origin. At an ultrastructural level, the endothelial lining of the newly formed microvessels showed diaphragmatic fenestration, a characteristic feature of endothelial cells of pancreatic islets in situ. On the basis of these findings we suggest that pancreatic islet transplantation may take a unique position in the field of organ transplantation, since the generally proposed mechanisms of endothelial cell-dependent antigen recognition as a trigger of graft rejection may not be transferred to islet grafts, containing microvessels lined by endothelial cells of host origin.

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Selected References

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

  1. Albelda S. M., Muller W. A., Buck C. A., Newman P. J. Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule. J Cell Biol. 1991 Sep;114(5):1059–1068. doi: 10.1083/jcb.114.5.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albelda S. M., Oliver P. D., Romer L. H., Buck C. A. EndoCAM: a novel endothelial cell-cell adhesion molecule. J Cell Biol. 1990 Apr;110(4):1227–1237. doi: 10.1083/jcb.110.4.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ausprunk D. H., Knighton D. R., Folkman J. Vascularization of normal and neoplastic tissues grafted to the chick chorioallantois. Role of host and preexisting graft blood vessels. Am J Pathol. 1975 Jun;79(3):597–618. [PMC free article] [PubMed] [Google Scholar]
  4. Ballinger W. F., Lacy P. E. Transplantation of intact pancreatic islets in rats. Surgery. 1972 Aug;72(2):175–186. [PubMed] [Google Scholar]
  5. Bonner-Weir S., Orci L. New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes. 1982 Oct;31(10):883–889. doi: 10.2337/diab.31.10.883. [DOI] [PubMed] [Google Scholar]
  6. Brockmeyer C., Ulbrecht M., Schendel D. J., Weiss E. H., Hillebrand G., Burkhardt K., Land W., Gokel M. J., Riethmüller G., Feucht H. E. Distribution of cell adhesion molecules (ICAM-1, VCAM-1, ELAM-1) in renal tissue during allograft rejection. Transplantation. 1993 Mar;55(3):610–615. doi: 10.1097/00007890-199303000-00027. [DOI] [PubMed] [Google Scholar]
  7. Demarchez M., Hartmann D. J., Prunieras M. An immunohistological study of the revascularization process in human skin transplanted onto the nude mouse. Transplantation. 1987 Jun;43(6):896–903. [PubMed] [Google Scholar]
  8. Endrich B., Asaishi K., Götz A., Messmer K. Technical report--a new chamber technique for microvascular studies in unanesthetized hamsters. Res Exp Med (Berl) 1980;177(2):125–134. doi: 10.1007/BF01851841. [DOI] [PubMed] [Google Scholar]
  9. Forbes R. D., Guttmann R. D. Evidence for complement-induced endothelial injury in vivo: a comparative ultrastructural tracer study in a controlled model of hyperacute rat cardiac allograft rejection. Am J Pathol. 1982 Mar;106(3):378–387. [PMC free article] [PubMed] [Google Scholar]
  10. Fuggle S. V., Sanderson J. B., Gray D. W., Richardson A., Morris P. J. Variation in expression of endothelial adhesion molecules in pretransplant and transplanted kidneys--correlation with intragraft events. Transplantation. 1993 Jan;55(1):117–123. doi: 10.1097/00007890-199301000-00022. [DOI] [PubMed] [Google Scholar]
  11. Griffith R. C., Scharp D. W., Hartman B. K., Ballinger W. F., Lacy P. E. A morphologic study of intrahepatic portal-vein islet isografts. Diabetes. 1977 Mar;26(3):201–214. doi: 10.2337/diab.26.3.201. [DOI] [PubMed] [Google Scholar]
  12. Kvietys P. R., Perry M. A., Granger D. N. Permeability of pancreatic capillaries to small molecules. Am J Physiol. 1983 Oct;245(4):G519–G524. doi: 10.1152/ajpgi.1983.245.4.G519. [DOI] [PubMed] [Google Scholar]
  13. Lambert P. B. Vascularization of skin grafts. Nature. 1971 Jul 23;232(5308):279–280. doi: 10.1038/232279a0. [DOI] [PubMed] [Google Scholar]
  14. Lehr H. A., Hübner C., Finckh B., Angermüller S., Nolte D., Beisiegel U., Kohlschütter A., Messmer K. Role of leukotrienes in leukocyte adhesion following systemic administration of oxidatively modified human low density lipoprotein in hamsters. J Clin Invest. 1991 Jul;88(1):9–14. doi: 10.1172/JCI115309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leszczynski D., Schellekens H., Häyry P. Vascular endothelium in allograft rejection. Transplant Proc. 1988 Apr;20(2):262–263. [PubMed] [Google Scholar]
  16. Menger M. D., Jäger S., Walter P., Hammersen F., Messmer K. A novel technique for studies on the microvasculature of transplanted islets of Langerhans in vivo. Int J Microcirc Clin Exp. 1990 Feb;9(1):103–117. [PubMed] [Google Scholar]
  17. Menger M. D., Lehr H. A. Scope and perspectives of intravital microscopy--bridge over from in vitro to in vivo. Immunol Today. 1993 Nov;14(11):519–522. doi: 10.1016/0167-5699(93)90179-O. [DOI] [PubMed] [Google Scholar]
  18. Menger M. D., Vajkoczy P., Beger C., Messmer K. Orientation of microvascular blood flow in pancreatic islet isografts. J Clin Invest. 1994 May;93(5):2280–2285. doi: 10.1172/JCI117228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Menger M. D., Vajkoczy P., Leiderer R., Jäger S., Messmer K. Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts. J Clin Invest. 1992 Oct;90(4):1361–1369. doi: 10.1172/JCI116002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Menger M. D., Wolf B., Höbel R., Schorlemmer H. U., Messmer K. Microvascular phenomena during pancreatic islet graft rejection. Langenbecks Arch Chir. 1991;376(4):214–221. doi: 10.1007/BF00186815. [DOI] [PubMed] [Google Scholar]
  21. Platt J. L., Vercellotti G. M., Dalmasso A. P., Matas A. J., Bolman R. M., Najarian J. S., Bach F. H. Transplantation of discordant xenografts: a review of progress. Immunol Today. 1990 Dec;11(12):450–457. doi: 10.1016/0167-5699(90)90174-8. [DOI] [PubMed] [Google Scholar]
  22. Pyzdrowski K. L., Kendall D. M., Halter J. B., Nakhleh R. E., Sutherland D. E., Robertson R. P. Preserved insulin secretion and insulin independence in recipients of islet autografts. N Engl J Med. 1992 Jul 23;327(4):220–226. doi: 10.1056/NEJM199207233270402. [DOI] [PubMed] [Google Scholar]
  23. Samols E., Stagner J. I., Ewart R. B., Marks V. The order of islet microvascular cellular perfusion is B----A----D in the perfused rat pancreas. J Clin Invest. 1988 Jul;82(1):350–353. doi: 10.1172/JCI113593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scharp D. W., Lacy P. E., Santiago J. V., McCullough C. S., Weide L. G., Boyle P. J., Falqui L., Marchetti P., Ricordi C., Gingerich R. L. Results of our first nine intraportal islet allografts in type 1, insulin-dependent diabetic patients. Transplantation. 1991 Jan;51(1):76–85. doi: 10.1097/00007890-199101000-00012. [DOI] [PubMed] [Google Scholar]
  25. Skinner M. P., Lucas C. M., Burns G. F., Chesterman C. N., Berndt M. C. GMP-140 binding to neutrophils is inhibited by sulfated glycans. J Biol Chem. 1991 Mar 25;266(9):5371–5374. [PubMed] [Google Scholar]
  26. Stagner J. I., Samols E. The induction of capillary bed development by endothelial cell growth factor before islet transplantation may prevent islet ischemia. Transplant Proc. 1990 Apr;22(2):824–828. [PubMed] [Google Scholar]
  27. Tamatani T., Miyasaka M. Identification of monoclonal antibodies reactive with the rat homolog of ICAM-1, and evidence for a differential involvement of ICAM-1 in the adherence of resting versus activated lymphocytes to high endothelial cells. Int Immunol. 1990;2(2):165–171. doi: 10.1093/intimm/2.2.165. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Warnock G. L., Kneteman N. M., Ryan E. A., Rabinovitch A., Rajotte R. V. Long-term follow-up after transplantation of insulin-producing pancreatic islets into patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1992 Jan;35(1):89–95. doi: 10.1007/BF00400857. [DOI] [PubMed] [Google Scholar]
  30. Weir G. C., Bonner-Weir S., Leahy J. L. Islet mass and function in diabetes and transplantation. Diabetes. 1990 Apr;39(4):401–405. doi: 10.2337/diab.39.4.401. [DOI] [PubMed] [Google Scholar]
  31. van Suylichem P. T., Wolters G. H., van Schilfgaarde R. Peri-insular presence of collagenase during islet isolation procedures. J Surg Res. 1992 Nov;53(5):502–509. doi: 10.1016/0022-4804(92)90097-j. [DOI] [PubMed] [Google Scholar]

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