An immunohistochemical and immunoelectron microscopic study of adhesion molecules in synovial pannus formation in rheumatoid arthritis (original) (raw)

Abstract

To investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohistochemical and immunoelectron microscopic studies with monoclonal antibodies against the adhesion molecules, CD54 (ICAM-1), CD 11a (LFA-1), CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), Cdw49d (VLA-4) and CDw49e (VLA-5), were carried out to determine the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction. Treatment with anti-ICAM-1 resulted in membrane staining of most of the macrophages and fibroblasts infiltrating the synovial tissue and bordering the pannus-cartilage junction, suggesting the possibility that ICAM-1 may function to facilitate the adhesion of synovial type A cells bearing ICAM-1 to type B cells of the pannus. ICAM-1-positive macrophages and fibroblasts were often found to be in contact with lymphoid cells, suggesting also that a cellular immune reaction occurs in the formation of the pannus. In addition, VLA-3, VLA-4 and, particularly, VLA-5 were the predominant_β_1 integrins expressed by rheumatoid synovial pannus. Since these three integrins all function as fibronectin receptors, it is possible that the fibronectin-rich environment of the rheumatoid cartilage surface effectively traps pannus cells expressing high levels of these molecules. The VLA-5 molecule was found in a pericellular and interterritorial matrix distribution in the present study, strongly suggesting that a recepfor-ligand interaction between VLA-5 and cartilage matrix may occur at the early stage of pannus formation. Furthermore, an increase in_β_1 integrin may be necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to increased attachment.

Access this article

Log in via an institution

Subscribe and save

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Fassbender HG (1984) Is pannus a residue of inflammation? Arthritis Rheum 27:956
    PubMed Google Scholar
  2. Harris ED Jr, Glauert AM, Murley AHG (1977) Intracellular collagen fibers at the panmus-cartilage junction in rheumatoid arthritis. Arthritis Rheum 20:657–664
    PubMed Google Scholar
  3. Ishikawa H, Hirata S, Nishibayashi Y, Imura S, Kubo H, Ohno O (1994) The role of adhesion molecules in synovial pannus formation in rheumatoid arthritis. Clin Orthop Rel Res 300:297–303
    Google Scholar
  4. Klareskog L, Johnell O, Hulth A (1984) Expression of HLA-DR and HLA-DQ antigens on cells within the cartilage-pannus junction in rheumatoid arthritis. Rheumatol Int 4[Suppl]:11–15
    PubMed Google Scholar
  5. Kobayashi I, Ziff M (1975) Electron microscopic studies of cartilage-pannus junction in rheumatoid arthritis. Arthritis Rheum 18:475–483
    PubMed Google Scholar
  6. Lavietes BB, Diamond HS, Carson SE (1987) Possible contribution of cartilage to fibrous panmus. Arthritis Rheum 30:119–120
    PubMed Google Scholar
  7. Mitrovic D (1985) The mechanism of cartilage destruction in rheumatoid arthritis. Arthritis Rheum 28:1192–1193
    PubMed Google Scholar
  8. Muirden KD, Allard SA, Rogers K, Maini RN (1988) Immunoelectron microscopy of chondrocytes-derived cells in the rheumatoid cartilage parmus junction. Rheumatol Int 8:231–234
    PubMed Google Scholar
  9. Ishikawa H, Smiley JD, Ziff M (1975) Electron microscopic demonstration of immunoglobulin deposition in rheumatoid cartilage. Arthritis Rheum 18:563–576
    PubMed Google Scholar
  10. Ishikawa H (1988) Relationship between HLA-DR positive cells and different subsets in rheumatoid synovial membrane. J Orthop Rheumatol 1:146–158
    Google Scholar
  11. Ishikawa H, Ohno O, Saura R, Matsubara T, Kuroda T, Hirohata K (1991) Cytokine enhancement of monocyte/synovial cell attachment to the surface of cartilage: a possible trigger of pannus formation in arthritis. Rheumatol Int 11:31–36
    PubMed Google Scholar
  12. Ishikawa H, Hirata S, Nishibayashi Y, Kubo H, Ohno O, Imura S (1993) Cytokine enhancement of adhesion molecule expression on cultured synovial cells at the surface of cartilage. A pos sible trigger of parmus formation in arthritis. Arthritis Rheum 36:9 (S265)
    Google Scholar
  13. Elices MJ, Hemler ME (1989) The human integrin VLA-2 is a collagen receptor on some cells and collagen/laminin receptor on others. Proc Natl Acad Sci USA 85:9906–9910
    Google Scholar
  14. Elices MJ, Osborn L, Takada Y, Crouse C, Lubowsij S, Hemler ME, Lobb RR (1990) VCAM-1 on activated endothelium interacts with the leukocytes Integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 60:577–584
    PubMed Google Scholar
  15. Garcia-Vicuna R, Humbria A, Posigo AA, Lopez-Elzaurdia C, De Landauri MO, Sanchez-Madrid F, Laffon A (1992) VLA family in rheumatoid arthritis: evidence for in vivo regulated adhe sion of synovial fluid T cells to fibronectin through VLA-5 Integrin. Clin Exp Immunol 88:435–441
    PubMed Google Scholar
  16. Hynes RD (1987) Integrins; a family of cell surface receptors. Cell 85:549–554
    Google Scholar
  17. Ramachandrula A, Tiku K, Tiku ML (1992) Tripeptide RGDdependent adhesion of articular chondrocytes to synovial fibroblasts. J Clin Sci 101:859–871
    Google Scholar
  18. Ishikawa H, Hirata S, Nishibayashi Y, Kubo H, Saura R, Imura S (1994) The role of adhesion molecules in synovial parmus formation in rheumatoid arthritis: an immunohistochemical and im munoelectron microscopic study. Arthritis Rheum 37:9(S):311
    Google Scholar
  19. Kurosaka M, Ziff M (1983) Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium. J Exp Med 158:1191–1210
    PubMed Google Scholar
  20. Cosimi AB, Geoffrion C, Anderson T, Conti D, Anderson DC, Rosenthal AS, Rothlein R (eds) (1989) Leukocyte adhesion molecules. Springer, New York, pp 274–289
    Google Scholar
  21. Loeser RF (1993) Integrin-mediated attachment of articular chondrocytes to extracellular matrix proteins. Arthritis Rheum 36:1103–1110
    PubMed Google Scholar
  22. Simmons D, Makgoba MW, Seed B (1988) ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature 331:624
    PubMed Google Scholar
  23. Woods VL Jr, Schreck PJ, Gesnik DS (1994) Integrin expression by human articular chondrocytes. Arthritis Rheum 37:537–544
    PubMed Google Scholar
  24. Alberda SM, Buck CA (1990) Integrins and other cell adhesion molecules. FASEB 4:2868–2880
    PubMed Google Scholar
  25. Hemler HE, Huang C, Takada Y, Schwarz L, Strominger JL, Clabby ML (1987) Characterization of the cell surface heterodimer VLA-4 and related peptide. J Biol Chem 262:11478–11485
    PubMed Google Scholar
  26. Ishikawa H, Hirata S, Nishibayashi Y, Kubo H, Nannbae M, Ohno O, Imura S (1994) Role of adhesion molecules in the lymphoid cell distribution in rheumatoid synovial membrane. Rheumatol Int 13:229–236
    Google Scholar
  27. Hanley J, Pledger D, Parkhill W, Roberts M, Gross M (1990) Phenotypic characterization of dissociated mononuclear cells from rheumatoid synovial membrane. Rheumatol Int 17:1274–1279
    Google Scholar
  28. Laffon A, Garcia-Vincuna R, Humbria A, Posigo AA, Corbi AL, de Landaruli MO, Sanchez-Madrid F (1991) Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis. J Clin Invest 88:546–552
    PubMed Google Scholar
  29. Pitzalis C, Kingsley G, Panayi G (1994) Adhesion molecules in rheumatoid arthritis: role in the pathogenesis and prospects for therapy. Ann Rheum Dis 53:287–288
    PubMed Google Scholar
  30. Rodriquets RM, Pitzalis C, Kingsley GH, Henderson E, Humphries MJ (1992) T-lymphocyte adhesion to fibronectin: a possible mechanism for T cell accumulation in the rheumatoid joint. Clin Exp Immunol 89:439–445
    PubMed Google Scholar
  31. El-Gabalawy H, Wikins J (1993) PI (CD29) integrin expression in rheumatoid synovial membrane: an immunohistologic study of distribution pattern. J Rheumatol 20:231–237
    PubMed Google Scholar
  32. Koch AE, Burrows JC, Heines GK, Carlos TM, Harlan JM, Leibovich SJ (1991) Immunolocalization of endothelial and leukocyte adhesion molecules in rheumatoid and osteoarthritic synovial tissues. Lab Invest 64:312–320
    Google Scholar
  33. Ishikawa H, Ziff M (1976) Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane. Arthritis Rheum 19:1–14
    PubMed Google Scholar
  34. Tak PP, Thurkow EW, Daha M, Kluin PM, Smeets TIM, Meinders AE, Breedveld FC (1995) Expression of adhesion molecules in early rheumatoid synovial tissue. Clin Pathol Immunopathol 77:236–242
    Google Scholar
  35. Hemler ME (1990) VLA proteins in the integrin family: structure, functions, and their role on leukocytes. Ann Rev Immunol 8:365–400
    Google Scholar
  36. Shiozawa S, Shiozawa K, Fujita T (1983) Morphologic observations in the early phase of the cartilage-pannus junction. Arthritis Rheum 26:472–478
    PubMed Google Scholar
  37. Salter DM, Hughes DE, Simpson R, Gardner DC (1992) Integrin expression by human articular chondrocytes. Br J Rheumatol 31:231–234
    PubMed Google Scholar
  38. Brown RA, Fones KC (1990) The synthesis and accumulation of fibronectin by human articular cartilage. J Rheumatol 17:65–72
    PubMed Google Scholar
  39. Mollenhauer J, Bee JA, Lixarbe MA, von der Mark K (1984) Role of anchorin C II, a 31,000-mol-wt membrane protein, in the interaction of chondrocytes with type II collagen. J Cell Biol 98:1572–1578
    PubMed Google Scholar

Download references

Author information

Authors and Affiliations

  1. Faculty of Health Science, Kobe University School of Medicine, 7-chome, Tomogaoka, Suma-ku, 654-01, Kobe, Japan
    H. Ishikawa & S. Hirata
  2. Department of Orthopaedic Surgery, Ishikawa Hospital, Himeji, Japan
    Y. Andoh
  3. Department of Orthopaedic Surgery, Kakogawa National Hospital, Kakogawa, Japan
    H. Kubo, N. Nakagawa & Y. Nishibayashi
  4. Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, Japan
    K. Mizuno

Authors

  1. H. Ishikawa
    You can also search for this author inPubMed Google Scholar
  2. S. Hirata
    You can also search for this author inPubMed Google Scholar
  3. Y. Andoh
    You can also search for this author inPubMed Google Scholar
  4. H. Kubo
    You can also search for this author inPubMed Google Scholar
  5. N. Nakagawa
    You can also search for this author inPubMed Google Scholar
  6. Y. Nishibayashi
    You can also search for this author inPubMed Google Scholar
  7. K. Mizuno
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Ishikawa, H., Hirata, S., Andoh, Y. et al. An immunohistochemical and immunoelectron microscopic study of adhesion molecules in synovial pannus formation in rheumatoid arthritis.Rheumatol Int 16, 53–60 (1996). https://doi.org/10.1007/BF01816436

Download citation

Key words