Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Jun;86(11):4282–4286. doi: 10.1073/pnas.86.11.4282

Intercellular adhesion molecule 1 is induced on isolated endocrine islet cells by cytokines but not by reovirus infection.

I L Campbell 1, A Cutri 1, D Wilkinson 1, A W Boyd 1, L C Harrison 1
PMCID: PMC287435  PMID: 2498883

Abstract

The selective destruction of the pancreatic islet beta cells in type 1 diabetes mellitus is thought to be mediated by a cellular autoimmune process, possibly triggered by virus infection in genetically susceptible individuals. Because of the potentially important role of cell-cell adhesion in the immune response, we investigated whether cytokine products of mononuclear cells, or virus infection, induced the expression of intercellular adhesion molecule 1 (ICAM-1) on human endocrine islet cells. By flow cytofluorimetry, control islet cells did not express detectable ICAM-1. However, after a 72-hr exposure of islets to interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) (each at 250 units/ml), ICAM-1 was induced on greater than 85% of islet cells. IFN-gamma was 50% more potent than TNF-alpha; together, their effects were additive. Class I major histocompatibility complex (MHC) protein expression, detected on control islet cells, was also stimulated by IFN-gamma and/or TNF-alpha. In contrast, infection with reovirus type 3 did not induce ICAM-1 on islet cells, although it stimulated the expression of class I MHC proteins. By double-label indirect immunofluorescence microscopy, ICAM-1 expression was identified on both beta (insulin-secreting) and delta (somatostatin-secreting) islet cells. Monoclonal antibody to ICAM-1 precipitated protein of Mr 97,000 from [35S]methionine-labeled islets exposed to IFN-gamma and TNF-alpha, but not from control islets. RNA blot analysis revealed a major species of 3.3 kilobases and a minor species of 2.2 kilobases induced in islets exposed to the cytokines. These findings have implications for the molecular mechanisms of beta-cell destruction in type 1 diabetes, in that expression of ICAM-1 by beta cells may facilitate adhesion of antigen-targeted immune cells.

Full text

PDF
4284

Images in this article

4285Image
on p.4285
4285Image
on p.4285
4285Image
on p.4285
4285Image
on p.4285
4285Image
on p.4285
4285Image
on p.4285
4286Image
on p.4286
4286Image
on p.4286

Selected References

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

  1. Assan R., Bach J. F., Czernichow P., Dupré J., Stiller C. R., Eisenbarth G. S., Gries F. A., Kolb H., Harrison L. C., Lafferty K. Immunosuppressive drugs in diabetes. Lancet. 1986 Nov 8;2(8515):1097–1097. doi: 10.1016/s0140-6736(86)90491-5. [DOI] [PubMed] [Google Scholar]
  2. Blue M. L., Craig K. A., Anderson P., Branton K. R., Jr, Schlossman S. F. Evidence for specific association between class I major histocompatibility antigens and the CD8 molecules of human suppressor/cytotoxic cells. Cell. 1988 Jul 29;54(3):413–421. doi: 10.1016/0092-8674(88)90204-8. [DOI] [PubMed] [Google Scholar]
  3. Bottazzo G. F. Beta-cell damage in diabetic insulitis: are we approaching a solution? Diabetologia. 1984 Apr;26(4):241–249. doi: 10.1007/BF00283644. [DOI] [PubMed] [Google Scholar]
  4. Bottazzo G. F., Dean B. M., McNally J. M., MacKay E. H., Swift P. G., Gamble D. R. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. 1985 Aug 8;313(6):353–360. doi: 10.1056/NEJM198508083130604. [DOI] [PubMed] [Google Scholar]
  5. Boyd A. W., Wawryk S. O., Burns G. F., Fecondo J. V. Intercellular adhesion molecule 1 (ICAM-1) has a central role in cell-cell contact-mediated immune mechanisms. Proc Natl Acad Sci U S A. 1988 May;85(9):3095–3099. doi: 10.1073/pnas.85.9.3095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burstin S. J., Spriggs D. R., Fields B. N. Evidence for functional domains on the reovirus type 3 hemagglutinin. Virology. 1982 Feb;117(1):146–155. doi: 10.1016/0042-6822(82)90514-1. [DOI] [PubMed] [Google Scholar]
  7. Campbell I. L., Harrison L. C., Ashcroft R. G., Jack I. Reovirus infection enhances expression of class I MHC proteins on human beta-cell and rat RINm5F cell. Diabetes. 1988 Mar;37(3):362–365. doi: 10.2337/diab.37.3.362. [DOI] [PubMed] [Google Scholar]
  8. Campbell I. L., Iscaro A., Harrison L. C. IFN-gamma and tumor necrosis factor-alpha. Cytotoxicity to murine islets of Langerhans. J Immunol. 1988 Oct 1;141(7):2325–2329. [PubMed] [Google Scholar]
  9. Campbell I. L., Oxbrow L., West J., Harrison L. C. Regulation of MHC protein expression in pancreatic beta-cells by interferon-gamma and tumor necrosis factor-alpha. Mol Endocrinol. 1988 Feb;2(2):101–107. doi: 10.1210/mend-2-2-101. [DOI] [PubMed] [Google Scholar]
  10. Campbell I. L., Wong G. H., Schrader J. W., Harrison L. C. Interferon-gamma enhances the expression of the major histocompatibility class I antigens on mouse pancreatic beta cells. Diabetes. 1985 Nov;34(11):1205–1209. doi: 10.2337/diab.34.11.1205. [DOI] [PubMed] [Google Scholar]
  11. Chesnut R. W., Colon S. M., Grey H. M. Antigen presentation by normal B cells, B cell tumors, and macrophages: functional and biochemical comparison. J Immunol. 1982 Apr;128(4):1764–1768. [PubMed] [Google Scholar]
  12. Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Lymphocyte function-associated antigen 1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4535–4539. doi: 10.1073/pnas.78.7.4535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): mechanism of blockade of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions. J Immunol. 1981 Aug;127(2):590–595. [PubMed] [Google Scholar]
  14. Dougherty G. J., Murdoch S., Hogg N. The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immune response. Eur J Immunol. 1988 Jan;18(1):35–39. doi: 10.1002/eji.1830180107. [DOI] [PubMed] [Google Scholar]
  15. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  16. Eisenbarth G. S. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986 May 22;314(21):1360–1368. doi: 10.1056/NEJM198605223142106. [DOI] [PubMed] [Google Scholar]
  17. Foulis A. K., Farquharson M. A. Aberrant expression of HLA-DR antigens by insulin-containing beta-cells in recent-onset type I diabetes mellitus. Diabetes. 1986 Nov;35(11):1215–1224. doi: 10.2337/diab.35.11.1215. [DOI] [PubMed] [Google Scholar]
  18. Foulis A. K., Liddle C. N., Farquharson M. A., Richmond J. A., Weir R. S. The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia. 1986 May;29(5):267–274. doi: 10.1007/BF00452061. [DOI] [PubMed] [Google Scholar]
  19. Gepts W., Lecompte P. M. The pancreatic islets in diabetes. Am J Med. 1981 Jan;70(1):105–115. doi: 10.1016/0002-9343(81)90417-4. [DOI] [PubMed] [Google Scholar]
  20. Gray D. W., McShane P., Grant A., Morris P. J. A method for isolation of islets of Langerhans from the human pancreas. Diabetes. 1984 Nov;33(11):1055–1061. doi: 10.2337/diab.33.11.1055. [DOI] [PubMed] [Google Scholar]
  21. Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kupfer A., Swain S. L., Singer S. J. The specific direct interaction of helper T cells and antigen-presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells. J Exp Med. 1987 Jun 1;165(6):1565–1580. doi: 10.1084/jem.165.6.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. Makgoba M. W., Sanders M. E., Ginther Luce G. E., Dustin M. L., Springer T. A., Clark E. A., Mannoni P., Shaw S. ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells. Nature. 1988 Jan 7;331(6151):86–88. doi: 10.1038/331086a0. [DOI] [PubMed] [Google Scholar]
  25. Makgoba M. W., Sanders M. E., Ginther Luce G. E., Gugel E. A., Dustin M. L., Springer T. A., Shaw S. Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1-dependent adhesion in T cell-mediated cytotoxicity. Eur J Immunol. 1988 Apr;18(4):637–640. doi: 10.1002/eji.1830180423. [DOI] [PubMed] [Google Scholar]
  26. Mandrup-Poulsen T., Bendtzen K., Dinarello C. A., Nerup J. Human tumor necrosis factor potentiates human interleukin 1-mediated rat pancreatic beta-cell cytotoxicity. J Immunol. 1987 Dec 15;139(12):4077–4082. [PubMed] [Google Scholar]
  27. Martz E. Mechanism of specific tumor-cell lysis by alloimmune T lymphocytes: resolution and characterization of discrete steps in the cellular interaction. Contemp Top Immunobiol. 1977;7:301–361. doi: 10.1007/978-1-4684-3054-7_9. [DOI] [PubMed] [Google Scholar]
  28. Onodera T., Jenson A. B., Yoon J. W., Notkins A. L. Virus-induced diabetes mellitus: reovirus infection of pancreatic beta cells in mice. Science. 1978 Aug 11;201(4355):529–531. doi: 10.1126/science.208156. [DOI] [PubMed] [Google Scholar]
  29. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  30. Pujol-Borrell R., Todd I., Doshi M., Bottazzo G. F., Sutton R., Gray D., Adolf G. R., Feldmann M. HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin. Nature. 1987 Mar 19;326(6110):304–306. doi: 10.1038/326304a0. [DOI] [PubMed] [Google Scholar]
  31. Rothlein R., Dustin M. L., Marlin S. D., Springer T. A. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986 Aug 15;137(4):1270–1274. [PubMed] [Google Scholar]
  32. Samson M., Cousin J. L., Fehlmann M. Cross-linking of insulin receptors to MHC antigens in human B lymphocytes: evidence for selective molecular interactions. J Immunol. 1986 Oct 1;137(7):2293–2298. [PubMed] [Google Scholar]
  33. Schreiber A. B., Schlessinger J., Edidin M. Interaction between major histocompatibility complex antigens and epidermal growth factor receptors on human cells. J Cell Biol. 1984 Feb;98(2):725–731. doi: 10.1083/jcb.98.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sibley R. K., Sutherland D. E., Goetz F., Michael A. F. Recurrent diabetes mellitus in the pancreas iso- and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab Invest. 1985 Aug;53(2):132–144. [PubMed] [Google Scholar]
  35. Simmons D., Makgoba M. W., Seed B. ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature. 1988 Feb 18;331(6157):624–627. doi: 10.1038/331624a0. [DOI] [PubMed] [Google Scholar]
  36. Staunton D. E., Marlin S. D., Stratowa C., Dustin M. L., Springer T. A. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell. 1988 Mar 25;52(6):925–933. doi: 10.1016/0092-8674(88)90434-5. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES