Skip to main content
Immunology logoLink to Immunology
. 1993 Jan;78(1):50–57.

Extracellular matrix induces tumour necrosis factor-alpha secretion by an interaction between resting rat CD4+ T cells and macrophages.

R Hershkoviz 1, D Gilat 1, S Miron 1, Y A Mekori 1, D Aderka 1, D Wallach 1, I Vlodavsky 1, I R Cohen 1, O Lider 1
PMCID: PMC1421774  PMID: 8094710

Abstract

T lymphocytes and macrophages (M phi) have been seen to accumulate at sites of lesions in blood vessel walls, suggesting that these cells may contribute to the pathogenesis of inflammatory reactions. Tumour necrosis factor-alpha (TNF-alpha), a cytokine produced by both M phi and T lymphocytes, plays a major role in inflammatory reactions, blood vessel formation, thrombosis and atherosclerosis. We now report that secretion of TNF-alpha by cloned CD4+ rat T cells, and to a lesser degree by peripheral T cells, and M phi can be induced in vitro in the absence of antigen, in a major histocompatibility complex (MHC) class II-independent manner by integrin-mediated recognition of immobilized components of extracellular matrix such as fibronectin and laminin; the secretion of TNF-alpha by the interacting resting cells on fibronectin was partially abrogated by the presence of the Arg-Gly-Asp (RGD)-containing amino acid sequence. This T cell-M phi interaction involves CD2 and CD4 molecules and requires a signal transduced in the T cells by a protein tyrosine kinase. Thus, a multicellular interaction with extracellular matrix protein exposed as a consequence of vascular wall injury can serve to signal the secretion of TNF-alpha which induces the recruitment of additional immune cells to the developing lesion.

Full text

PDF
50

Selected References

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

  1. Barath P., Fishbein M. C., Cao J., Berenson J., Helfant R. H., Forrester J. S. Detection and localization of tumor necrosis factor in human atheroma. Am J Cardiol. 1990 Feb 1;65(5):297–302. doi: 10.1016/0002-9149(90)90291-8. [DOI] [PubMed] [Google Scholar]
  2. Ben-Nun A., Wekerle H., Cohen I. R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur J Immunol. 1981 Mar;11(3):195–199. doi: 10.1002/eji.1830110307. [DOI] [PubMed] [Google Scholar]
  3. Beutler B., Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625–655. doi: 10.1146/annurev.iy.07.040189.003205. [DOI] [PubMed] [Google Scholar]
  4. Clark S. J., Law D. A., Paterson D. J., Puklavec M., Williams A. F. Activation of rat T lymphocytes by anti-CD2 monoclonal antibodies. J Exp Med. 1988 Jun 1;167(6):1861–1872. doi: 10.1084/jem.167.6.1861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cybulsky M. I., Gimbrone M. A., Jr Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991 Feb 15;251(4995):788–791. doi: 10.1126/science.1990440. [DOI] [PubMed] [Google Scholar]
  6. Dustin M. L., Springer T. A. Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol. 1988 Jul;107(1):321–331. doi: 10.1083/jcb.107.1.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eierman D. F., Johnson C. E., Haskill J. S. Human monocyte inflammatory mediator gene expression is selectively regulated by adherence substrates. J Immunol. 1989 Mar 15;142(6):1970–1976. [PubMed] [Google Scholar]
  8. Eldor A., Fuks Z., Levine R. F., Vlodavsky I. Measurement of platelet and megakaryocyte interaction with the subendothelial extracellular matrix. Methods Enzymol. 1989;169:76–91. doi: 10.1016/0076-6879(89)69051-9. [DOI] [PubMed] [Google Scholar]
  9. Fridman R., Lider O., Naparstek Y., Fuks Z., Vlodavsky I., Cohen I. R. Soluble antigen induces T lymphocytes to secrete an endoglycosidase that degrades the heparan sulfate moiety of subendothelial extracellular matrix. J Cell Physiol. 1987 Jan;130(1):85–92. doi: 10.1002/jcp.1041300113. [DOI] [PubMed] [Google Scholar]
  10. Hershkoviz R., Miron S., Cohen I. R., Miller A., Lider O. T lymphocyte adhesion to the fibronectin and laminin components of the extracellular matrix is regulated by the CD4 molecule. Eur J Immunol. 1992 Jan;22(1):7–13. doi: 10.1002/eji.1830220103. [DOI] [PubMed] [Google Scholar]
  11. Larson R. S., Springer T. A. Structure and function of leukocyte integrins. Immunol Rev. 1990 Apr;114:181–217. doi: 10.1111/j.1600-065x.1990.tb00565.x. [DOI] [PubMed] [Google Scholar]
  12. Lider O., Mekori Y. A., Miller T., Bar-Tana R., Vlodavsky I., Baharav E., Cohen I. R., Naparstek Y. Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell-mediated immunity. Eur J Immunol. 1990 Mar;20(3):493–499. doi: 10.1002/eji.1830200306. [DOI] [PubMed] [Google Scholar]
  13. Meuer S. C., Hussey R. E., Fabbi M., Fox D., Acuto O., Fitzgerald K. A., Hodgdon J. C., Protentis J. P., Schlossman S. F., Reinherz E. L. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
  14. Miyake K., Underhill C. B., Lesley J., Kincade P. W. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med. 1990 Jul 1;172(1):69–75. doi: 10.1084/jem.172.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mustelin T., Coggeshall K. M., Isakov N., Altman A. T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation. Science. 1990 Mar 30;247(4950):1584–1587. doi: 10.1126/science.2138816. [DOI] [PubMed] [Google Scholar]
  16. Ofosu-Appiah W., Warrington R. J., Morgan K., Wilkins J. A. Lymphocyte extracellular matrix interactions. Induction of interferon by connective tissue components. Scand J Immunol. 1989 May;29(5):517–525. doi: 10.1111/j.1365-3083.1989.tb01154.x. [DOI] [PubMed] [Google Scholar]
  17. Pacifici R., Basilico C., Roman J., Zutter M. M., Santoro S. A., McCracken R. Collagen-induced release of interleukin 1 from human blood mononuclear cells. Potentiation by fibronectin binding to the alpha 5 beta 1 integrin. J Clin Invest. 1992 Jan;89(1):61–67. doi: 10.1172/JCI115586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pacifici R., Carano A., Santoro S. A., Rifas L., Jeffrey J. J., Malone J. D., McCracken R., Avioli L. V. Bone matrix constituents stimulate interleukin-1 release from human blood mononuclear cells. J Clin Invest. 1991 Jan;87(1):221–228. doi: 10.1172/JCI114975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rosoff P. M., Burakoff S. J., Greenstein J. L. The role of the L3T4 molecule in mitogen and antigen-activated signal transduction. Cell. 1987 Jun 19;49(6):845–853. doi: 10.1016/0092-8674(87)90622-2. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Rudd C. E. CD4, CD8 and the TCR-CD3 complex: a novel class of protein-tyrosine kinase receptor. Immunol Today. 1990 Nov;11(11):400–406. doi: 10.1016/0167-5699(90)90159-7. [DOI] [PubMed] [Google Scholar]
  22. Ruddle N. H., Bergman C. M., McGrath K. M., Lingenheld E. G., Grunnet M. L., Padula S. J., Clark R. B. An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med. 1990 Oct 1;172(4):1193–1200. doi: 10.1084/jem.172.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ruoslahti E. Fibronectin and its receptors. Annu Rev Biochem. 1988;57:375–413. doi: 10.1146/annurev.bi.57.070188.002111. [DOI] [PubMed] [Google Scholar]
  24. Shimizu Y., Shaw S. Lymphocyte interactions with extracellular matrix. FASEB J. 1991 Jun;5(9):2292–2299. doi: 10.1096/fasebj.5.9.1860621. [DOI] [PubMed] [Google Scholar]
  25. Shimizu Y., Van Seventer G. A., Horgan K. J., Shaw S. Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. Nature. 1990 May 17;345(6272):250–253. doi: 10.1038/345250a0. [DOI] [PubMed] [Google Scholar]
  26. Shimizu Y., van Seventer G. A., Horgan K. J., Shaw S. Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. J Immunol. 1990 Jul 1;145(1):59–67. [PubMed] [Google Scholar]
  27. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  28. Trevillyan J. M., Lu Y. L., Atluru D., Phillips C. A., Bjorndahl J. M. Differential inhibition of T cell receptor signal transduction and early activation events by a selective inhibitor of protein-tyrosine kinase. J Immunol. 1990 Nov 15;145(10):3223–3230. [PubMed] [Google Scholar]
  29. Wallach D. Preparations of lymphotoxin induce resistance to their own cytotoxic effect. J Immunol. 1984 May;132(5):2464–2469. [PubMed] [Google Scholar]
  30. Webb D. S., Shimizu Y., Van Seventer G. A., Shaw S., Gerrard T. L. LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science. 1990 Sep 14;249(4974):1295–1297. doi: 10.1126/science.1697984. [DOI] [PubMed] [Google Scholar]
  31. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  32. Yamada A., Nikaido T., Nojima Y., Schlossman S. F., Morimoto C. Activation of human CD4 T lymphocytes. Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor. J Immunol. 1991 Jan 1;146(1):53–56. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES