Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1991 Apr;138(4):1045–1057.

Balloon catheter de-endothelialization of the nude rat carotid. Response to injury in the absence of functional T lymphocytes.

G A Ferns 1, M A Reidy 1, R Ross 1
PMCID: PMC1886114  PMID: 1849358

Abstract

The development of an intimal proliferative lesion after balloon catheter de-endothelialization was studied in congenitally athymic nude rats lacking T lymphocytes. Significant intimal thickening was observed in both the homozygous (nu/nu) and euthymic heterozygous (nu/+) animals 6 days after injury, which increased further after 10 days. There was no significant difference in mean intimal:medial cross-sectional area between the nu/nu and nu/+ animals at either time. Approximately 1% of the cells in the neointima of both groups of animals were leukocytes (OX-1 positive); 0.7% were macrophages (ED-1 positive). In neither nu/nu nor nu/+ animals did T lymphocytes (OX-19-positive cells) constitute more than 0.1% of the neointimal cell population. These data suggest that T lymphocytes do not play a significant role in the accumulation of neointimal cells. The presence of macrophages within the lesions raises the possibility that they may be involved in the recruitment and proliferation of smooth muscle cells. In vitro characterization of nu/nu carotid medial smooth muscle cells demonstrated approximately 500,000 binding sites for platelet-derived growth factor (PDGF)-BB and few PDGF-AA binding sites (less than 10,000). The mitogenic and chemotactic responses of these cells to the three dimeric forms of PDGF correlated with this receptor subunit distribution. Platelet-derived growth factor accounted for approximately 50% of the mitogenic activity of a rat platelet releasate. Platelet-derived growth factor-BB and PDGF-AB were both potent chemotactic agents for the nude rat carotid smooth muscle cells with a peak response at approximately 10 ng/ml. In contrast, PDGF-AA, transforming growth factor beta, and basic fibroblast growth factor were only weak chemoattractants for these cells.

Full text

PDF
1045

Images in this article

1053Figure 7
on p.1053
1049Figure 1
on p.1049
1050Figure 2
on p.1050
1051Figure 3
on p.1051
1052Figure 5
on p.1052
1052Figure 6
on p.1052
1054Figure 8
on p.1054

Selected References

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

  1. Barclay A. N. The localization of populations of lymphocytes defined by monoclonal antibodies in rat lymphoid tissues. Immunology. 1981 Apr;42(4):593–600. [PMC free article] [PubMed] [Google Scholar]
  2. Bowen-Pope D. F., Hart C. E., Seifert R. A. Sera and conditioned media contain different isoforms of platelet-derived growth factor (PDGF) which bind to different classes of PDGF receptor. J Biol Chem. 1989 Feb 15;264(5):2502–2508. [PubMed] [Google Scholar]
  3. Brooks C. G., Webb P. J., Robins R. A., Robinson G., Baldwin R. W., Festing M. F. Studies on the immunobiology of rnu/rnu "nude" rats with congenital aplasia of the thymus. Eur J Immunol. 1980 Jan;10(1):58–65. doi: 10.1002/eji.1830100112. [DOI] [PubMed] [Google Scholar]
  4. Clowes A. W., Reidy M. A., Clowes M. M. Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest. 1983 Sep;49(3):327–333. [PubMed] [Google Scholar]
  5. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  6. Emeson E. E., Robertson A. L., Jr T lymphocytes in aortic and coronary intimas. Their potential role in atherogenesis. Am J Pathol. 1988 Feb;130(2):369–376. [PMC free article] [PubMed] [Google Scholar]
  7. Ferns G. A., Sprugel K. H., Seifert R. A., Bowen-Pope D. F., Kelly J. D., Murray M., Raines E. W., Ross R. Relative platelet-derived growth factor receptor subunit expression determines cell migration to different dimeric forms of PDGF. Growth Factors. 1990;3(4):315–324. doi: 10.3109/08977199009003674. [DOI] [PubMed] [Google Scholar]
  8. Ferns G., Reidy M., Ross R. Vascular effects of cyclosporine A in vivo and in vitro. Am J Pathol. 1990 Aug;137(2):403–413. [PMC free article] [PubMed] [Google Scholar]
  9. Festing M. F., May D., Connors T. A., Lovell D., Sparrow S. An athymic nude mutation in the rat. Nature. 1978 Jul 27;274(5669):365–366. doi: 10.1038/274365a0. [DOI] [PubMed] [Google Scholar]
  10. Hansson G. K., Holm J., Jonasson L. Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol. 1989 Jul;135(1):169–175. [PMC free article] [PubMed] [Google Scholar]
  11. Hansson G. K., Holm J., Kral J. G. Accumulation of IgG and complement factor C3 in human arterial endothelium and atherosclerotic lesions. Acta Pathol Microbiol Immunol Scand A. 1984 Nov;92(6):429–435. doi: 10.1111/j.1699-0463.1984.tb04424.x. [DOI] [PubMed] [Google Scholar]
  12. Hansson G. K., Jonasson L., Holm J., Claesson-Welsh L. Class II MHC antigen expression in the atherosclerotic plaque: smooth muscle cells express HLA-DR, HLA-DQ and the invariant gamma chain. Clin Exp Immunol. 1986 May;64(2):261–268. [PMC free article] [PubMed] [Google Scholar]
  13. Hansson G. K., Jonasson L., Holm J., Clowes M. M., Clowes A. W. Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro. Circ Res. 1988 Oct;63(4):712–719. doi: 10.1161/01.res.63.4.712. [DOI] [PubMed] [Google Scholar]
  14. Hosang M. Recombinant interferon-gamma inhibits the mitogenic effect of platelet-derived growth factor at a level distal to the growth factor receptor. J Cell Physiol. 1988 Mar;134(3):396–404. doi: 10.1002/jcp.1041340310. [DOI] [PubMed] [Google Scholar]
  15. Jonasson L., Holm J., Hansson G. K. Cyclosporin A inhibits smooth muscle proliferation in the vascular response to injury. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2303–2306. doi: 10.1073/pnas.85.7.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jonasson L., Holm J., Skalli O., Bondjers G., Hansson G. K. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis. 1986 Mar-Apr;6(2):131–138. doi: 10.1161/01.atv.6.2.131. [DOI] [PubMed] [Google Scholar]
  17. Majesky M. W., Reidy M. A., Bowen-Pope D. F., Hart C. E., Wilcox J. N., Schwartz S. M. PDGF ligand and receptor gene expression during repair of arterial injury. J Cell Biol. 1990 Nov;111(5 Pt 1):2149–2158. doi: 10.1083/jcb.111.5.2149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Masuda J., Ross R. Atherogenesis during low level hypercholesterolemia in the nonhuman primate. I. Fatty streak formation. Arteriosclerosis. 1990 Mar-Apr;10(2):164–177. doi: 10.1161/01.atv.10.2.164. [DOI] [PubMed] [Google Scholar]
  19. Minick C. R., Alonso D. R., Rankin L. Role of immunologic arterial injury in atherogenesis. Thromb Haemost. 1978 Apr 30;39(2):304–311. [PubMed] [Google Scholar]
  20. Minick C. R., Murphy G. E. Experimental induction of atheroarteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. II. Effect of repeatedly injected foreign protein in rabbits fed a lipid-rich, cholesterol-poor diet. Am J Pathol. 1973 Nov;73(2):265–300. [PMC free article] [PubMed] [Google Scholar]
  21. Munro J. M., van der Walt J. D., Munro C. S., Chalmers J. A., Cox E. L. An immunohistochemical analysis of human aortic fatty streaks. Hum Pathol. 1987 Apr;18(4):375–380. doi: 10.1016/s0046-8177(87)80168-5. [DOI] [PubMed] [Google Scholar]
  22. Richards K. L., McCullough J. A modified microchamber method for chemotaxis and chemokinesis. Immunol Commun. 1984;13(1):49–62. doi: 10.3109/08820138409025449. [DOI] [PubMed] [Google Scholar]
  23. Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
  24. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  25. Seifert P. S., Kazatchkine M. D. The complement system in atherosclerosis. Atherosclerosis. 1988 Oct;73(2-3):91–104. doi: 10.1016/0021-9150(88)90030-5. [DOI] [PubMed] [Google Scholar]
  26. Seifert R. A., Hart C. E., Phillips P. E., Forstrom J. W., Ross R., Murray M. J., Bowen-Pope D. F. Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem. 1989 May 25;264(15):8771–8778. [PubMed] [Google Scholar]
  27. Steiniger B., Schröder D., Lück R., Luciano L., van der Meide P. H. Gamma interferon treatment in vivo provokes accumulation of activated monocytes in the venous circulation of rats. Am J Pathol. 1990 Apr;136(4):967–978. [PMC free article] [PubMed] [Google Scholar]
  28. Vaessen L. M., Broekhuizen R., Rozing J., Vos J. G., Schuurman H. J. T-cell development during ageing in congenitally athymic (nude) rats. Scand J Immunol. 1986 Aug;24(2):223–235. doi: 10.1111/j.1365-3083.1986.tb02089.x. [DOI] [PubMed] [Google Scholar]
  29. Vaessen L. M., Broekhuizen R., Vos J. G., Schuurman H. J., Rozing J. "T-cells" in nude rats. Adv Exp Med Biol. 1985;186:313–321. [PubMed] [Google Scholar]
  30. Verheyen A. K., Vlaminckx E. M., Lauwers F. M., Saint-Guillain M. L., Borgers M. J. Identification of macrophages in intimal thickening of rat carotid arteries by cytochemical localization of purine nucleoside phosphorylase. Arteriosclerosis. 1988 Nov-Dec;8(6):759–767. doi: 10.1161/01.atv.8.6.759. [DOI] [PubMed] [Google Scholar]
  31. Vlaicu R., Niculescu F., Rus H. G., Cristea A. Immunohistochemical localization of the terminal C5b-9 complement complex in human aortic fibrous plaque. Atherosclerosis. 1985 Nov;57(2-3):163–177. doi: 10.1016/0021-9150(85)90030-9. [DOI] [PubMed] [Google Scholar]
  32. Vos J. G., Berkvens J. M., Kruijt B. C. The athymic nude rat. I. Morphology of lymphoid and endocrine organs. Clin Immunol Immunopathol. 1980 Feb;15(2):213–228. doi: 10.1016/0090-1229(80)90032-x. [DOI] [PubMed] [Google Scholar]
  33. Vos J. G., Kreeftenberg J. G., Kruijt B. C., Kruizinga W., Steerenberg P. The athymic nude rat. II. Immunological characteristics. Clin Immunol Immunopathol. 1980 Feb;15(2):229–237. doi: 10.1016/0090-1229(80)90033-1. [DOI] [PubMed] [Google Scholar]
  34. Walker L. N., Bowen-Pope D. F., Ross R., Reidy M. A. Production of platelet-derived growth factor-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7311–7315. doi: 10.1073/pnas.83.19.7311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. van der Wal A. C., Das P. K., Bentz van de Berg D., van der Loos C. M., Becker A. E. Atherosclerotic lesions in humans. In situ immunophenotypic analysis suggesting an immune mediated response. Lab Invest. 1989 Aug;61(2):166–170. [PubMed] [Google Scholar]

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

RESOURCES