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. 1992 Jun 1;89(11):5157–5161. doi: 10.1073/pnas.89.11.5157

Transduction of a foreign histocompatibility gene into the arterial wall induces vasculitis.

E G Nabel 1, G Plautz 1, G J Nabel 1
PMCID: PMC49248  PMID: 1594626

Abstract

Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis.

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Selected References

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

  1. Bjorkman P. J., Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem. 1990;59:253–288. doi: 10.1146/annurev.bi.59.070190.001345. [DOI] [PubMed] [Google Scholar]
  2. Bleicher P. A., Balk S. P., Hagen S. J., Blumberg R. S., Flotte T. J., Terhorst C. Expression of murine CD1 on gastrointestinal epithelium. Science. 1990 Nov 2;250(4981):679–682. doi: 10.1126/science.1700477. [DOI] [PubMed] [Google Scholar]
  3. Danos O., Mulligan R. C. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460–6464. doi: 10.1073/pnas.85.17.6460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ellis S. A., Taylor C., McMichael A. Recognition of HLA-B27 and related antigen by a monoclonal antibody. Hum Immunol. 1982 Aug;5(1):49–59. doi: 10.1016/0198-8859(82)90030-1. [DOI] [PubMed] [Google Scholar]
  5. Hall S., Barr W., Lie J. T., Stanson A. W., Kazmier F. J., Hunder G. G. Takayasu arteritis. A study of 32 North American patients. Medicine (Baltimore) 1985 Mar;64(2):89–99. [PubMed] [Google Scholar]
  6. Korman A. J., Frantz J. D., Strominger J. L., Mulligan R. C. Expression of human class II major histocompatibility complex antigens using retrovirus vectors. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2150–2154. doi: 10.1073/pnas.84.8.2150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Libby P., Hansson G. K. Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. Lab Invest. 1991 Jan;64(1):5–15. [PubMed] [Google Scholar]
  8. Lim C. S., Chapman G. D., Gammon R. S., Muhlestein J. B., Bauman R. P., Stack R. S., Swain J. L. Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog. Circulation. 1991 Jun;83(6):2007–2011. doi: 10.1161/01.cir.83.6.2007. [DOI] [PubMed] [Google Scholar]
  9. Lovett E. J., 3rd, Schnitzer B., Keren D. F., Flint A., Hudson J. L., McClatchey K. D. Application of flow cytometry to diagnostic pathology. Lab Invest. 1984 Feb;50(2):115–140. [PubMed] [Google Scholar]
  10. Nabel E. G., Plautz G., Boyce F. M., Stanley J. C., Nabel G. J. Recombinant gene expression in vivo within endothelial cells of the arterial wall. Science. 1989 Jun 16;244(4910):1342–1344. doi: 10.1126/science.2499928. [DOI] [PubMed] [Google Scholar]
  11. Nabel E. G., Plautz G., Nabel G. J. Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science. 1990 Sep 14;249(4974):1285–1288. doi: 10.1126/science.2119055. [DOI] [PubMed] [Google Scholar]
  12. Plautz G., Nabel E. G., Nabel G. J. Introduction of vascular smooth muscle cells expressing recombinant genes in vivo. Circulation. 1991 Feb;83(2):578–583. doi: 10.1161/01.cir.83.2.578. [DOI] [PubMed] [Google Scholar]
  13. Plautz G., Nabel E. G., Nabel G. J. Selective elimination of recombinant genes in vivo with a suicide retroviral vector. New Biol. 1991 Jul;3(7):709–715. [PubMed] [Google Scholar]
  14. Prescott M. F., McBride C. K., Court M. Development of intimal lesions after leukocyte migration into the vascular wall. Am J Pathol. 1989 Nov;135(5):835–846. [PMC free article] [PubMed] [Google Scholar]
  15. Shelhamer J. H., Volkman D. J., Parrillo J. E., Lawley T. J., Johnston M. R., Fauci A. S. Takayasu's arteritis and its therapy. Ann Intern Med. 1985 Jul;103(1):121–126. doi: 10.7326/0003-4819-103-1-121. [DOI] [PubMed] [Google Scholar]
  16. Volkman D. J., Mann D. L., Fauci A. S. Association between Takayasu's arteritis and a B-cell alloantigen in North Americans. N Engl J Med. 1982 Feb 25;306(8):464–465. doi: 10.1056/NEJM198202253060806. [DOI] [PubMed] [Google Scholar]
  17. Wilson J. M., Birinyi L. K., Salomon R. N., Libby P., Callow A. D., Mulligan R. C. Implantation of vascular grafts lined with genetically modified endothelial cells. Science. 1989 Jun 16;244(4910):1344–1346. doi: 10.1126/science.2734614. [DOI] [PubMed] [Google Scholar]

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