Skip to main content
SpringerLink
Log in

Synoviocytes in chronic synovitis in situ and cytokine stimulated synovial cells in vitro neo-express α1, α3 and α5 chains of β1 integrins

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The expression of the β1 integrins was examined immunohistochemically in synoviocytes from normal synovial membrane and from chronic synovitis of different aetiology and intensity. Normal synoviocytes were α6β1-positive but lacked α1 through α5. In mild inflammation type A synoviocytes neo-expressed α1, α3, and α5 chains. In severe inflammation both type A and B synoviocytes expressed α3, α4, α5, and α6 chains. The effects of inflammatory cytokines, as single agents or in combination, on the β1 integrin expression in cultured normal synoviocytes was determined by immunocytochemistry and flow cytometry. The α1 chain, while absent in unstimulated synoviocytes, was induced by interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and interferon-γ (INF-γ). This effect was enhanced by combining IL-1β and TNF-α. Expression of the α3 chain was up-regulated by IL-1β and, more intensely, by IFN-γ. Transforming growth factor β (TGF-β) inhibited the up-regulating effect of IL-1β and antagonized the effect of IFN-γ on α3 chain expression. Expression of the α5 chain was up-regulated significantly by co-stimulation through IL-1β together with TGF-β or TNF-α. Thus, the β1 integrin profile of cytokine activated synoviocytes in vitro resembled that of synoviocytes in synovitis in situ. These data suggest that IL-1β, TNF-α, IFN-γ, and TGF-β are likely to be among the effectors regulating β1 integrin expression in synoviocytes in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Albelda SM (1993) Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest 68:4–17

    Google Scholar 

  2. Albelda SMC, Burck A (1990) Integrins and other cell adhesion molecules. FASEB J 4:2868–2880

    CAS  PubMed  Google Scholar 

  3. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, Howell D, Kaplan D, Koopman W, Longley SIII, Mankin H, McShane DJ, Medsger T Jr, Meenan R, Mikkelsen W, Moskowitz R, Murphy W, Rothschild B, Segal M, Sokoloff L, Wolfe F (1986) Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum 29:1039–1049

    CAS  PubMed  Google Scholar 

  4. Amiot M, Bernard A, Tran HC, Leca G, Kanellopoulos JM, Boumsell L (1986) The human cell surface glycoprotein complex (gp 120, 200) recognized by monoclonal antibody K20 is a component binding to phytohaemagglutinin on T cells. Scand J Immunol 23:109–118

    Google Scholar 

  5. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healy LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller G, Sharp JT, Wilder RL, Hunder GG (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    CAS  PubMed  Google Scholar 

  6. Barland P, Novikoff AB, Hamerman D (1962) Electron microscopy of the human synovial membrane. J Cell Biol 14:207–220

    Google Scholar 

  7. Bauvois B, Rouillard D, Sanceau J, Wietzerbin J (1992) IFN-γ and transforming growth factor-β1 differently regulate fibronectin and laminin receptors of human differentiating monocytic cells. J Immunol 148:3912–3919

    Google Scholar 

  8. Bucala R, Ritchlin C, Winchester R, Cerami A (1991) Constitutive production of inflammatory and mitogenic cytokines by rheumatoid synovial fibroblasts. J Exp Med 173:569–574

    Google Scholar 

  9. Burmester GR, Dimitriu-Bona A, Waters SJ, Winchester RJ (1983) Identification of three major synovial lining cell populations by monoclonal antibodies directed to Ia antigens and antigens associated with monocytes/macrophages and fibroblasts. Scand J Immunol 17:69–82

    Google Scholar 

  10. Campanero MR, Arroyo AG, Pulido R, Ursa A, de Matias MS, Sánchez-Mateos P, Kassner PD, Chan BMC, Hemler ME, Corbí AL, de Landázuri MO, Sánchez-Madrid F (1992) Functional role of α2β1 and α4β1 integrins in leukocyte intercellular adhesion induced through the common β1 subunit. Eur J Immunol 22:3111–3119

    Google Scholar 

  11. Carter WG, Ryan MC, Gahr P (1991) Epiligrin, a new cell adhesion ligand for integrin α3β1 in epithelial basement membranes. Cell 65:599–610

    Google Scholar 

  12. Defilippi P, van Hinsbergh V, Bertolotto A, Rossino P, Silengo L, Tarone G (1991) Differential distribution and modulation of expression of alpha1/beta1 integrin on human endothelial cells. J Cell Biol 114:855–863

    Google Scholar 

  13. Demaziere A, Athanasou NA (1992) Adhesion receptors of intimal and subintimal cells of the normal synovial membrane. J Pathol 168:209–215

    Google Scholar 

  14. DiCorleto PE, Bowen-Pope DF (1983) Cultured endothelial cells produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci USA 80:1919–1923

    Google Scholar 

  15. El-Gabalawy H, Wilkins J (1993) β1 (CD29) integrin expression in rheumatoid synovial membranes: an immunohistologic study of distribution patterns. J Rheumatol 20:231–237

    Google Scholar 

  16. Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyi S, Hemler ME, Lobb RR (1990) VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 60:577–584

    Google Scholar 

  17. Enenstein J, Waleh NS, Kramer RH (1992) Basic FGF and TGF-β differentially modulate integrin expression of human microvascular endothelial cells. Exp Cell Res 203:499–503

    Google Scholar 

  18. Fietz T, Laqué M, Henne C, Möller P, Koretz K. α2β1 integrin is a tenascin receptor on colon carcinoma cell lines mediating adhesion (submitted)

  19. Firestein GS, Alvaro-Garcia JM, Maki R (1990) Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol 144:3347–3353

    Google Scholar 

  20. Fradet Y, Cordon-Cardo C, Thomson T, Daly ME, Whitmore WF, Lloyd KO, Melamed MR, Old LJ (1984) Cell surface antigens of human bladder cancer defined by mouse monoclonal antibodies. Proc Natl Acad Sci USA 81:224–228

    Google Scholar 

  21. Giltay JC, Brinkman HJ, Modderman PW, von dem Borne AEGKr, van Mourik JA (1989) Human vascular endothelial cells express a membrane protein complex immunochemically indistinguishable from platelet VLA-2 (glycoprotein Ia-IIa) complex. Blood 73:1235–1241

    Google Scholar 

  22. Goddard DH, Grossman SL, Williams WV, Weiner DB, Gross JL, Eidsvoog K, Dasch JR (1992) Regulation of synovial cell growth. Co-expression of transforming growth factor-β and basic fibroblast growth factor by cultured synovial cells. Arthritis Rheum 35:1296–1303

    Google Scholar 

  23. Heino J, Massagué J (1988) Transforming growth factor-β switches the pattern of integrins expressed in MG-63 human osteosarcoma cells and causes a selective loss of cell adhesion to laminin. J Biol Chem 264:21806–21811

    Google Scholar 

  24. Heino J, Ignotz RA, Hemler ME, Crouse C, Massagué J (1989) Regulation of cell adhesion receptors by transforming growth factor-β. Concordant regulation of integrins that share a common β1 subunit. J Biol Chem 264:380–388

    Google Scholar 

  25. Hemler ME, Jacobson JG, Brener MB, Mann D, Strominger JL (1985) VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. Eur J Immunol 15:502–508

    Google Scholar 

  26. Hemler ME, Elices MJ, Parker C, Takada Y (1990) Structure of the integrin VLA-4 and its cell-cell and cell-matrix adhesion functions. Immunol Rev 114:45–65

    Google Scholar 

  27. Holers VM, Ruff TG, Parks DL, McDonald JA, Ballard LL, Brown EJ (1989) Molecular cloning of a murine fibronectin receptor and its expression during inflammation. Expression of VLA-5 is increased in activated peritoneal macrophages in a manner discordant from major histocompatibility complex class II. J Exp Med 169:1689–1605

    Google Scholar 

  28. Hopkins SH, Meager A (1988) Cytokines in synovial fluid: II. The presence of tumor necrosis factor and interferon. Clin Exp Immunol 73:88–92

    Google Scholar 

  29. Hynes RO (1992) Integrins: versatility, modulation, and signalling in cell adhesion. Cell 69:11–25

    Article  CAS  PubMed  Google Scholar 

  30. Johnson BA, Haines GK, Harlow LA, Koch AE (1993) Adhesion molecule expression in human synovial tissue. Arthritis Rheum 36:137–146

    Google Scholar 

  31. Lipsky PE, Davis LS, Cush JJ, Oppenheimer-Marks N (1989) The role of cytokines in the pathogenesis of rheumatoid arthritis. Springer Semin Immunopathol 11:123–162

    Google Scholar 

  32. Miossec P, Cavender D, Ziff M (1986) Production of interleukin 1 by human endothelial cells. J Immunol 136:2486–2491

    Google Scholar 

  33. Nikkari L, Aho A, Yli-Jama T, Larjava H, Jalkanen M, Heino J (1993) Expression of integrin family of cell adhesion receptors in rheumatoid synovium. Alpha 6 integrin subunit in normal and hyperplastic synovial lining cell layer. Am J Pathol 142:1019–1027

    Google Scholar 

  34. Pulido R, Elices MJ, Campanero MR, Osborn L, Schiffer S, Garcia-Pardo A, Lobb R, Hemler ME, Sanchez-Madrid F (1991) Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. J Biol Chem 166:10241–10245

    Google Scholar 

  35. Sanchez-Madrid F, de Landazuri MO, Morago G, Cebrian M, Acevedo A, Bernabeiu C (1986) VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization. Eur J Immunol 16:1343–1349

    Google Scholar 

  36. Santala P, Heino J (1991) Regulation of integrin-type cell adhesion receptors by cytokines. J Biol Chem 266:23505–23509

    Google Scholar 

  37. Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC, Gospodarowicz D (1987) Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature 325:257–259

    Google Scholar 

  38. Seth R, Salcedo R, Patarroyo M, Makgoba MW (1991) ICAM-2 peptides mediate lymphocyte adhesion by binding to CD11a/CD18 and CD49d/CD29 integrins. FEBS Lett 282:193–196

    Google Scholar 

  39. Sonnenberg A, Jansen H, Hogervorst F, Calafat J, Hilgers J (1987) A complex of platelet glycoprotein Ic and IIa identified by a rat monoclonal antibody. J Biol Chem 21:10376–10383

    Google Scholar 

  40. Sriramarao P, Mendler M, Boudon MA (1993) Endothelial cell attachment and spreading on human tenascin is mediated by α2β1 and αvβ3 integrins. J Cell Science 105:1001–1012

    Google Scholar 

  41. Symington BE, Symington FW, Rohrschneider LR (1989) Phorbol ester induces increased expression, altered glycosylation, and reduced adhesion of K562 erythroleukemia cell fibronectin receptors. J Biol Chem 264:13258–13266

    Google Scholar 

  42. Velde A te, Klomp JPG, Yard BA, Vries JE de, Figdor CG (1988) Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4. J Immunol 140:1548–1554

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine V, Hospitalstraße 3, D-69115, Heidelberg, Germany

    N. Rinaldi

  2. Institute of Pathology, Im Neuenheimer Feld 220, D-69120, Heidelberg, Germany

    T. Barth, C. Henne, G. Mechtersheimer & P. Möller

Authors
  1. N. Rinaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Barth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Henne
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Mechtersheimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Möller
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rinaldi, N., Barth, T., Henne, C. et al. Synoviocytes in chronic synovitis in situ and cytokine stimulated synovial cells in vitro neo-express α1, α3 and α5 chains of β1 integrins. Vichows Archiv A Pathol Anat 425, 171–180 (1994). https://doi.org/10.1007/BF00230354

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00230354

Key words

Search

Navigation