Skip to main content
Log in

Cell Adhesion Molecules in Rheumatoid Arthritis

Implications for Therapy

  • Review Article
  • Clinical Pharmacology
  • Published:
Drugs & Aging Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Summary

Rheumatoid arthritis is a systemic inflammatory disease of the joints and major internal organs that has an unknown aetiology. Cell adhesion molecules (CAMs) are expressed on the surface of cells, enabling homotypic and heterotypic cell-cell interactions that are fundamental in the process of the inflammatory reaction.

Three major families of CAMs are now recognised, with numerous subtypes. Many of these molecules play an important role in the mechanism of disease in rheumatoid arthritis. E-Selectin and intercellular adhesion molecule (ICAM)-l are upregulated on the synovial endothelium, while vascular cell adhesion molecule (VCAM)-l plays an important role in the synovial lining layer cells and within the synovial stroma.

The expression of CAMs may be blocked by monoclonal antibodies and modified by nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs. This has very important implications in the therapy of rheumatoid arthritis.

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

Access this article

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. Pincus T. Rheumatoid arthritis: disappointing long term outcomes despite successful clinical trials. J Clin Epidemiol 1988; 41: 1037–41

    Article  PubMed  CAS  Google Scholar 

  2. Harlan JM. Leukocyte-endothelial interactions. Blood 1994; 84(7): 2068–101

    PubMed  Google Scholar 

  3. Rothlein R, Dustin ML, Marlin SD, et al. A human intercellular adhesion molecule distinct from LFA-1. J Immunol 1986; 137: 1270–4

    PubMed  CAS  Google Scholar 

  4. Osborn L, Hession C, Tizard R, et al. Direct expression cloning of vascular cell adhesion molecule-1, a cytokine induced endothelial protein that binds to lymphocytes. Cell 1989; 59: 1203–11

    Article  PubMed  CAS  Google Scholar 

  5. Springer TA. Adhesion receptors of the immune system. Nature 1990; 346: 425–34

    Article  PubMed  CAS  Google Scholar 

  6. Hale LP, Martin ME, McCollum DE, et al. Immunohistologic analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment. Arthritis Rheum 1989; 32: 22–30

    Article  PubMed  CAS  Google Scholar 

  7. Veale D, Yanni G, Rogers S, et al. Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis compared with rheumatoid arthritis. Arthritis Rheum 1993; 36: 893–900

    Article  PubMed  CAS  Google Scholar 

  8. Johnson BA, Haines GK, Harlow LA, et al. Adhesion molecule expression in human synovial tissue. Arthritis Rheum 1993; 36: 137–46

    Article  PubMed  CAS  Google Scholar 

  9. Mulherin D, Veale D, Belch JJF, et al. Adhesion molecule expression in untreated inflammatory arthritis. Q J Med 1996; 89: 195–203

    Article  CAS  Google Scholar 

  10. Gearing JH, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993; 14: 506–12

    Article  PubMed  CAS  Google Scholar 

  11. Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 1991; 65: 859–73

    Article  PubMed  CAS  Google Scholar 

  12. Butcher EC. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 1991; 67: 1033–6

    Article  PubMed  CAS  Google Scholar 

  13. Smith MEF, Thomas JA. Cellular expression of lymphocyte function associated antigens and the intercellular adhesion molecule-1 in normal tissue. J Clin Pathol 1990; 43: 893–900

    Article  PubMed  CAS  Google Scholar 

  14. Dustin ML, Rothlein R, Bhan AK, et al. Induction by IL-1 and interferon γ: tissue distribution, biochemistry and functions of a natural adherence molecule (ICAM-1). J Immunol 1986; 137: 245–54

    PubMed  CAS  Google Scholar 

  15. Pober JS, Bevilacqua MP, Mendrick DL, et al. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce the biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 1986; 36: 1680–7

    Google Scholar 

  16. Aoki S, Imai K, Yachi A. Soluble intercellular adhesion molecule-1 (ICAM-1) antigen in patients with rheumatoid arthritis. Scand J Immunol 1993; 38: 485–90

    Article  PubMed  CAS  Google Scholar 

  17. Diamond MS, Staunton DE, De Fougerolles AR, et al. ICAM-1 (CD54): a counter receptor for Mac-1 (CD1 lb/CD18). J Cell Biol 1990; 111: 3129–39

    Article  PubMed  CAS  Google Scholar 

  18. Wallis WJ, Beatty PG, Ochs HD, et al. Human monocyte adherence to cultured vascular endothelium: monoclonal antibody-defined mechanisms. J Immunol 1985; 135: 2323–30

    PubMed  CAS  Google Scholar 

  19. Haskard DO, Cavender DE, Beatty P, et al. Cell adhesion to endothelial cells: mechanisms demonstrated by anti-LFA-1 monoclonal antibodies. J Immunol 1986; 137: 2901–6

    PubMed  CAS  Google Scholar 

  20. Arnaout MA. Leukocyte adhesion molecules deficiency: its structural basis, pathophysiology and implications for modulating the inflammatory response. Immunol Rev 1990; 114: 145–79

    Article  PubMed  CAS  Google Scholar 

  21. Bevilacqua MP, Nelson RM. Selectins. J Clin Invest 1993; 91: 379–87

    Article  PubMed  CAS  Google Scholar 

  22. Veale D, Rogers S, FitzGerald O. Immunolocalization of adhesion molecules in psoriatic arthritis, psoriatic and normal skin. Br J Dermatol 1995; 132: 32–8

    Article  PubMed  CAS  Google Scholar 

  23. Groves RW, Allen MH, Haskard DO, et al. Endothelial leukocyte adhesion molecule-1 (ELAM-1) expression in cutaneous inflammation. Br J Dermatol 1991; 124: 117–23

    Article  PubMed  CAS  Google Scholar 

  24. Polley MJ, Phillips ML, Wayner EW, et al. CD62 and endothelial leukocyte adhesion molecule-1 (ELAM-1) recognise the same carbohydrate ligand, sialyl-Lewis x. Proc Nat Acad Sei USA 1991; 88: 6224–8

    Article  CAS  Google Scholar 

  25. Veale DJ, Maple C, Kirk G, et al. Soluble cell adhesion molecule levels in rheumatoid arthritis in response to sulphasalazine therapy [abstract]. Arthritis Rheum 1995; 37(S370): 1299

    Google Scholar 

  26. Veale DJ, Kirk G, McLaren M, et al. Scleroderma skin score correlates with change in soluble ICAM-1 levels in response to endothelial stimulation [abstract]. Arthritis Rheum 1994; 37(S259): 596

    Google Scholar 

  27. Kavanaugh AF, Davis LS, Nichols LA, et al. Treatment of refractory rheumatoid arthritis with a monoclonal antibody to intercellular adhesion molecule-1. Arthritis Rheum 1994; 37: 992–9

    Article  PubMed  CAS  Google Scholar 

  28. Corkill MM, Kirkham BW, Haskard DO, et al. Gold treatment of rheumatoid arthritis decreases synovial expression of the endothelial leukocyte adhesion receptor ELAM-1. J Rheumatol 1991; 189(10): 1453–60

    Google Scholar 

  29. Cronstein BN, Van de Stowe M, Druska L, et al. Nonsteroidal antiinflammatory agents inhibit stimulated neutrophil adhesion to endothelium: adenosine dependent and independent mechanisms. Inflammation 1994; 18(3): 323–35

    Article  PubMed  CAS  Google Scholar 

  30. Kyan-Aung U, Lee TH, Haskard DO. The inhibitory effect of tenidap on leucocyte-endothelial cell adhesion. J Rheumatol 1993; 20(6): 1014–9

    PubMed  CAS  Google Scholar 

  31. Boschelli DH, Kramer JB, Khatana SS, et al. Inhibition of E-selectin-, ICAM-1-, and VCAM-1-mediated cell adhesion by benzo[b]thiophene-, benzofuran-, indole-, and naphthalene-2-carboxamides: identification of PD144795 as an anti-inflammatory agent. J Med Chem 1995; 38(22): 4597–614

    Article  PubMed  CAS  Google Scholar 

  32. Bator JM, Weitzberg M, Burch RM. N-[9H-(2,7-dimethyl-fluorenyl-9-methoxy)carbonyl]-L-leucine, NPC15669, prevents neutrophil adherence to endothelium and inhibits CD11b/CD18 upregulation. Immunopharmacology 1992; 23(2): 139–49

    Article  PubMed  CAS  Google Scholar 

  33. Wolle J, Ferguson F, Keshava C, et al. Inhibition of tumour necrosis factor induced human aortic endothelial cell adhesion molecule gene expression by an alkoxybenzo[b]thio-phene-2-carboxamide. Biochem Biophys Res Comm 1995; 214(1): 6–10

    Article  PubMed  CAS  Google Scholar 

  34. Diaz-Gonzalez F, Campanero MR, Mollinedo F, et al. Prevention of in vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs. J Clin Invest 1995; 95(4): 1756–65

    Article  PubMed  CAS  Google Scholar 

  35. Pitzalis C, Pipitone N, Lee A, et al. Corticosteroid (C) inhibition of T cell adhesion molecule expression in vivo depends on C-resistant/C-sensitive status [abstract]. Arthritis Rheum 1995; 38(S288): 812

    Google Scholar 

  36. Kavanaugh AF, Davis LS, Nichols LA, et al. Retreatment of rheumatoid arthritis patients with an anti-ICAM-1 monoclonal [abstract]. Arthritis Rheum 1995; 38(S280): 765

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Veale, D.J., Maple, C. Cell Adhesion Molecules in Rheumatoid Arthritis. Drugs & Aging 9, 87–92 (1996). https://doi.org/10.2165/00002512-199609020-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199609020-00003

Keywords

Navigation