Advertisement

Rheumatology International

, Volume 13, Issue 2, pp 71–75 | Cite as

Toxicity of complement for chondrocytes. A possible source of cartilage degradation in inflammatory arthritis

  • S. Satsuma
  • R. A. Scudamore
  • T. D. V. Cooke
  • W. P. Aston
  • R. Saura
Originals

Summary

Cartilage from patients with rheumatoid arthritis and from animals with antigen-induced arthritis is frequently contaminated with complement-containing immune complexes. A possible role for complement activation in cartilage degradation was modeled in vitro by exposing cultured bovine chondrocytes to homologous serum, and determining cytotoxicity by monitoring the release of intracellular 51Cr. Complement activation was found to be cytotoxic, having maximal effect at 20–30% serum by 18 h. Serum toxicity was ablated by heat (50°C, 20 min) or methylamine treatment but not by EGTA, suggesting that in these experiments activation occurred by the alternate route. The implications of the results are discussed in relation to ultrastructural evidence for the involvement of complement in the pathogenesis of cartilage degradation in inflammatory arthritis.

Key words

Chondrocyte Immune complex Cartilage Degradation Complement Cytotoxicity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mainardi CL (1987) Biochemical mechanisms of articular destruction. Rheum Dis Clin 13:215–233Google Scholar
  2. 2.
    Poole AR (1990) Enzymatic degradation: cartilage destruction. In: Brandt KD (ed) Cartilage changes in osteoarthritis. CIBA-Geigy/Indianapolis University School of Medicine, Indianapolis, pp 63–72Google Scholar
  3. 3.
    Mitchell N, Shepard N (1970) The ultrastructure of articular cartilage in rheumatoid arthritis. J Bone Joint Surg 52A:1405–1423Google Scholar
  4. 4.
    Dumonde DC, Glynn LE (1962) The production of arthritis in rabbits by an immunological reaction to fibrin. Br J Exp Pathol 43:373–383Google Scholar
  5. 5.
    Cooke TDV (1988) Antigen-induced arthritis, polyarthritis, and tenosynovitis. In: Greenwald RA, Diamond HS (eds) Handbook of animal models for the rheumatic diseases, vol. 1. CRC Press, Press, Boca Raton, Florida, pp 53–78Google Scholar
  6. 6.
    Sumi M, Maeda M, Cooke TDV (1986) Deleterious interactions of immune complexes with tibial cartilage of antigen-induced arthritic rabbits II. Chondrocyte degradation. Clin Orthop 212:260–274Google Scholar
  7. 7.
    Cooke TDV, Sumi M, Maeda M (1985) Deleterious interactions of immune complexes in cartilage of experimental immune arthritis 1. The erosion of pannus-free hyaline cartilage. Clin Orthop 183:235–245Google Scholar
  8. 8.
    McCarthy D, Goddard GH, Pell BK, Holborow EJ (1981) Intrinsically stable IgG aggregates. J Immunol Methods 41:63–74Google Scholar
  9. 9.
    Saura R, Uno K, Satsuma S, Kurz EU, Scudamore RA, Cooke TDV (1993) Mechanisms of cartilage destruction in inflammatory arthritis. Interactions between immunoglobulin and chondrocytes. J Reumatol 20:336–343Google Scholar
  10. 10.
    Cooke D, Saura R, Uno K, Scudamore A (1991) Interactions of immunoglobulins and chondrocytes. J Rheumatol 18 [Suppl 27]:114–116Google Scholar
  11. 11.
    Saura R, Cooke TDV, Scudamore RA, Satsuma S (1991) Cartilage destruction in rheumatoid arthritis: cytotoxicity of immunoglobulins and complement against chondrocytes. Trans Orthop Res Soc 16:337Google Scholar
  12. 12.
    Cooke TDV, Hurd ER, Jasin HE (1975) Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues. Arthritis Rheum 18:541–551Google Scholar
  13. 13.
    Vetto AA, Mannik M, Zatarain-Rios E, Wener MH (1990) Immune deposits in articular cartilage of patients with rheumatoid arthritis have a granular pattern not seen in osteoarthritis. Rheumatol Int 10:13–19Google Scholar
  14. 14.
    Ohno O, Cooke TDV (1978) Electromicroscopic morphology of immunoglobulin aggregates and their interactions in rheumatoid articular collagenous tissues. Arthritis Rheum 21:516–527Google Scholar
  15. 15.
    Kuettner KE, Pauli BU, Gall G, Memoli VA, Schenk RK (1982) Synthesis of cartilage matrix by mammalian chondrocytes in vitro. I. Isolation, culture characteristics, and morphology. J Cell Biol 93:743–750Google Scholar
  16. 16.
    Glowacki J, Trepman E, Folkman J (1983) Cell shape and phenotypic expression in chondrocytes. Proc Soc Exp Biol Med 172:93–98Google Scholar
  17. 17.
    Watt FM (1988) Effect of seeding density on stability of the differentiated phenotype of pig articular chondrocytes in culture. J Cell Sci 89:373–378Google Scholar
  18. 18.
    Pang ASD, Aston WP (1977) Alternative complement pathway in bovine serum: lysis of human erythrocytes. Am J Vet Res 38:355–359Google Scholar
  19. 19.
    Rapp HJ, Borsos T (1970) Reagents commonly used in complement research. In: Molecular basis of complement action. Appleton Centuary Crofts, New York, pp 75–109Google Scholar
  20. 20.
    Pang ASD, Aston WP (1978) The alternative complement pathway in bovine serum: the isolation of a serum protein with factor B activity. Immunochemistry 15:529–534Google Scholar
  21. 21.
    Mhatre A, Aston WP (1987) A simple hemolytic assay for bovine complement component C3. Vet Immunol 15:239–251Google Scholar
  22. 22.
    Sacks T, Moldow CF, Craddock PR, Bowers TK, Jacob HS (1978) Oxygen radicals mediated endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. J Clin Invest 61:1161–1167Google Scholar
  23. 23.
    Simon RH, Scoggin CH, Patterson D (1981) Hydrogen peroxide causes the fatal damage to human fibroblasts exposed to oxygen radicals. J Biol Chem 256:7181–7186Google Scholar
  24. 24.
    Weiss SJ, Young J, LoBuglio AF, Slivka A (1981) Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells. J Clin Invest 68:714–721Google Scholar
  25. 25.
    Saura R, Cooke TDV, Scudamore RA (1990) Matrix-degrading activity of chondrocytes stimulated by heat-aggregated IgG (abstract) Arthritis Rheum 33 [Suppl 5]:R40Google Scholar
  26. 26.
    Jacobs DB, Pipho C (1983) Use of propidium iodide staining and flow cytometry to measure antibody-mediated cytotoxicity: resolution of complement-sensitive and resistant target cells. J Immunol Methods 62:101–108Google Scholar
  27. 27.
    Muller-Eberhard HJ (1986) The membrane attack complex of complement. Ann Rev Immunol 4:503–528Google Scholar
  28. 28.
    Burger R, Hadding U, Schorlemmer HU, Brade V, Bitter-Suermann D (1975) Dextran sulfate: a synthetic activator of C3 via the alternative pathway. I. Influence of molecular size and degree of sulphation on the activation potency. Immunology 29: 549–554Google Scholar
  29. 29.
    Ruddy S, Austen KF (1970) The complement system in rheumatoid synovitis: 1. an analysis of complement component activities in rheumatoid synovial fluids. Arthritis Rheum 13: 713–723Google Scholar
  30. 30.
    Rodman WS, Williams RC, Bilka PJ, Muller-Eberhard HJ (1967) Immunofluorescent localization of the third and the fourth component of complement in synovial tissue from patients with rheumatoid arthritis. J Lab Clin Med 69:141–149Google Scholar
  31. 31.
    Partsch G, Bauer K, Broll H, Petera P, Dunky A, Meretey K (1991) Complement C3 cleavage product in synovial fluids detected by immunofixation. Z Rheumatol 50:82–85Google Scholar
  32. 32.
    Sanders ME, Kopicky JA, Wigley FM, Shin ML, Frank MM, Joiner KA (1986) Membrane attack comples of complement in rheumatoid synovial tissue demonstrated by immunofluorescent microscopy. J Rheumatol 13:1028–1034Google Scholar
  33. 33.
    Cooke TDV, Scudamore RA (1989) Studies in the pathogenesis of rheumatoid arthritis. 2: Antigen/antibody reactions with avascular joint tissues. Br J Rheumatol 28:333–340Google Scholar
  34. 34.
    Ostensen M, Stiansen R, Hetland G, Garred P (1991) Complement and complement receptors in human articular chondrocytes. In: Kuettner KE, Schleyerbach R, Peyron JG, Haskell VC (eds) Articular cartilage and osteoarthritis. Raven Press, New York p 706Google Scholar
  35. 35.
    Pettipher ER, Henderson B, Hardingham T, Ratcliffe A (1989) Cartilage proteoglycan depletion in acute and chronic antigen-induced arthritis. Arthritis Rheum 32:601–607Google Scholar
  36. 36.
    Harada T, Scudamore RA, Cooke TDV, Smith JT (1992) Deleterious interactions of immune complexes with cartilage in inflammatory arthritis. IV. Role of polymorphonuclear neutrophils. Eur J Exp Musculoskel Res 1:19–24Google Scholar
  37. 37.
    Hembry RM (1990) Rabbit models of arthritis: immunolocalization of metalloproteases and TIMP in synovium and cartilage. In: Knight GC, Wayman P (eds) The Stangeways Research Laboratory Cambridge. Annual Report 1990. Stangeways Research Laboratory, Cambridge, pp 26–30Google Scholar
  38. 38.
    Henderson B, Pettipher ER, Murphy G (1990) Metallo-proteinases and cartilage proteoglycan depletion in chronic arthritis. Arthritis Rheum 33:241–246Google Scholar
  39. 39.
    Iwasaki Y, Matsubara T, Hirohata K (1988) A mechanism of cartilage destruction in immunologically-mediated inflammation: increased superoxide anion release from chondrocytes in response to interleukin-1 and interferons. Orthop Trans 12:438Google Scholar
  40. 40.
    Saura R, Cooke TDV, Scudamore RA (1991) Superoxide generation by chondrocytes following stimulation by heat-aggregated IgG. Orthop Trans 15:177–178Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • S. Satsuma
    • 1
  • R. A. Scudamore
    • 1
  • T. D. V. Cooke
    • 1
  • W. P. Aston
    • 2
  • R. Saura
    • 1
  1. 1.Department of SurgeryQueen's UniversityKingstonCanada
  2. 2.Department of Microbiology and ImmunologyQueen's UniversityKingstonCanada

Personalised recommendations