Skip to main content
Log in

The possible role of neutrophil proteinases in damage to articular cartilage

  • Immunosuppression and Inflammation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

The proteolytic degradation of articular cartilage that is seen in the arthritides affects both of the major structural components of the tissue, proteoglycan and collagen. Neutrophil leucocytes are abundant in the synovial fluid of the inflamed joints, and we have considered whether the large quantities of neutral proteinases carried by these cells could contribute to the cartilage degradation. The two neutrophil serine proteinases have been isolated, and shown to break down both proteoglycan and collagen in articular cartilage. The enzymes attacked the non-helical terminal peptides of the collagen, eliminating the cross-links, thus destabilizing and solubilizing the fibres. The soluble collagen then denatured spontaneously, and was further degraded.

Although large quantities of the neutrophil proteinases are probably released in the synovial fluid each day, the inhibitory capacity of the fluid is seldom, if ever, saturated. Nevertheless, immunologically mediated release of the neutrophil enzymes in ‘frustrated endocytosis’ at the cartilage surface could give rise to the generalized damage that has been reported by others.

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. L.J. Ignarro,Regulation of Lysosomal Enzyme Secretion: Role in Inflammation, Agents and Actions4, 241–258 (1974).

    Google Scholar 

  2. A. Janoff, G. Feinstein, C.J. Malemud andJ.M. Elias,Degradation of Cartilage Proteoglycan by Human Leukocyte Granule Neutral Proteases — a Model of Joint Injury. II. Degradation of Isolated Bovine Nasal Cartilage Proteoglycan, J. Clin. Invest.57, 615–624 (1976).

    Google Scholar 

  3. A.L. Oronsky andC.W. Buermann,Phagocytic Release of Human Leukocyte Neutral Proteases. Analysis of Cartilage Degradation Products, Arch. Biochem. Biophys.176, 539–546 (1976).

    Google Scholar 

  4. Z.A. Cohn andE. Wiener, The Particulate Hydrolases of Macrophages. II. Biochemical and Morphological Response to Particle Ingestion. J. Exp. Med.118, 1009–1020 (1963).

    Google Scholar 

  5. G. Weissmann, R.B. Zurier, P.J. Speiler andI.M. Goldstein,Mechanisms of Lysosomal Enzyme Release from Leukocytes Exposed to Immune Complexes and Other Particles, J. Exp. Med.134, 149s-165s (1971).

    Google Scholar 

  6. P. Henson,Interaction of Cells with Immune Complexes, Adherence, Release of Constituents and Tissue Injury, J. Exp. Med.134, 114s-135s (1971).

    Google Scholar 

  7. P.M. Starkey, A.J. Barrett andM.C. Burleigh,The Degradation of Articular Collagen by Neutrophil Proteinases, Biochim. Biophys. Acta483, 386–397 (1977).

    Google Scholar 

  8. G. Murphy, J.J. Reynolds, U. Bretz andM. Baggiolini,Collagenase is a Component of the Specific Granules of Human Neutrophil Leucocytes, Biochem. J.162, 195–197 (1977).

    Google Scholar 

  9. B. Dewald, R. Rindler-Ludwig, U. Bretz andM. Baggiolini,Subcellular Localization and Heterogeneity of Neutral Proteases in Neutrophilic Polymorphonuclear Leukocytes, J. Exp. Med.141, 709–723 (1975).

    Google Scholar 

  10. P.M. Starkey andA.J. Barrett,Neutral Proteinases of Human Spleen. Purification and Criteria for Homogeneity of Elastase and Cathepsin G, Biochem. J.155, 255–263 (1976).

    Google Scholar 

  11. R. Baugh andJ. Travis,Human Leukocyte Granule Elastase: Rapid Isolation and Characterization, Biochemistry, U.S.A.15, 836–841 (1976).

    Google Scholar 

  12. E.D. Harris, Jr., H.G. Parker, E.L. Radin andS.M. Krane,Effects of Proteolytic Enzymes on Structural and Mechanical Properties of Cartilage, Arth. Rheum.15, 497–503 (1972).

    Google Scholar 

  13. G.E. Kempson, M.A. Tuke, J.T. Dingle, A.J. Barrett andP.H. Horsfield,The Effects of Proteolytic Enzymes on the Mechanical Properties of Adult Articular Cartilage, Biochim. Biophys. Acta428, 741–760 (1976).

    Google Scholar 

  14. T. Bitter andH.M. Muir,A Modified Uronic Acid Carbazole Reaction, Analyt. Biochem.4, 330–334 (1962).

    Google Scholar 

  15. M.C. Burleigh, A.J. Barrett andG.S. Lazarus,Cathepsin B1. A Lysosomal Enzyme that Degrades Native Collagen, Biochem. J.137, 387–398 (1974).

    Google Scholar 

  16. E.D. Harris, Jr. andS.M. Krane,An Endopeptidase from Rheumatoid Synovial Tissue Culture, Biochim. Biophys. Acta258, 566–576 (1972).

    Google Scholar 

  17. D.M. Neville,Molecular Weight Determination of Protein-Dodecyl Sulfate Complexes by Gel Electrophoresis in a Discontinuous Buffer System, J. Biol. Chem.246, 6328–6334 (1971).

    Google Scholar 

  18. D.R. Eyre andH. Muir,Characterization of the Major CNBr-Derived Peptides of Porcine Type II Collagen, Conn. Tiss. Res.3, 165–170 (1975).

    Google Scholar 

  19. H. Keiser, R.A. Greenwald, G. Feinstein andA. Janoff,Degradation of Cartilage Proteoglycan by Human Leukocyte Granule Neutral Proteases — a Model of Joint Injury. I. Penetration of Enzyme into Rabbit Articular Cartilage and Release of 35 SO 4 Labelled Material from the Tissue, J. Clin. Invest.57, 625–632 (1976).

    Google Scholar 

  20. A.J. Barrett andP.M. Starkey,The Possible Role of Leucocyte Proteinases in the Tissue Damage of Rheumatoid Arthritis, in:Rheumatoid Arthritis (Eds. J.L. Gordon and B.L. Hazleman; Elsevier/North-Holland Biomedical Press, Amsterdam, 1977), pp. 211–221.

    Google Scholar 

  21. P.J. Roughley andA.J. Barrett,The Degradation of Cartilage Proteoglycan by Tissue Proteinases. Proteoglycan Structure and its Susceptibility to Proteolysis, Biochem. J. (1977) (in press).

  22. P.J. Roughley,The Degradation of Cartilage Proteoglycans by Tissue Proteinases. Proteoglycan Heterogeneity and the Pathway of Proteolytic Degradation, Biochem. J. (1977) (in press).

  23. D.E. Woolley andJ.M. Evanson,Effect of Cartilage Proteoglycans on Human Collagenase Activities, Biochim. Biophys. Acta497, 144–150 (1977).

    Google Scholar 

  24. A. Maroudas, Cartilage Turnover, Ann. Rheum. Dis.34, Suppl. 55–57 (1975).

  25. A. Janoff,Mediators of Tissue Damage in Leukocyte Lysosomes. X. Further Studies on Human Granulocyte Elastase, Lab. Invest.22, 228–236 (1970).

    Google Scholar 

  26. A.J. Anderson,Enzyme System in Rat Leucocyte Granules which Degrades Insoluble Collagen, Ann. Rheum. Dis.30, 299–302 (1971).

    Google Scholar 

  27. G.S. Lazarus, J.R. Daniels, J. Lian andM.C. Burleigh,Role of Granulocyte Collagenase in Collagen Degradation, Amer. J. Path.68, 565–576 (1972).

    Google Scholar 

  28. I. Sopata, E. Wojtecka-Lukasik andA.M. Dancewicz,Solubilization of Collagen Fibrils by Human Leucocyte Collagenase Activated by Rheumatoid Synovial Fluid, Act Biochim. Polon.21, 283–289 (1974).

    Google Scholar 

  29. F.S. Steven, A. Torre-Blanco andJ.A.A. Hunter,A Neutral Protease in Rheumatoid Synovial Fluid Capable of Attacking the Telopeptide Regions of Polymeric Collagen Fibrils, Biochim. Biophys. Acta405, 188–200 (1975).

    Google Scholar 

  30. D.E. Woolley, K.A. Lindberg, R.W. Glanville andJ.M. Evanson,Action of Rheumatoid Synovial Collagenase on Cartilage Collagen. Different Susceptibilities of Cartilage and Tendon Collagen to Cartilage Attack, Eur. J. Biochem.50, 437–444 (1975).

    Google Scholar 

  31. T. Hayashi andY. Nagai,Effect of pH on the Stability of Collagen Molecule in Solution, J. Biochem.73, 999–1006 (1973).

    Google Scholar 

  32. C.I. Levene,The Hydrating Effect of Lathyrogenic Compounds on Chick-Embryo Cartilage in vitro, Biochem. J.101, 441–447 (1966).

    Google Scholar 

  33. W. Traub andK.R. Piez,The Chemistry and Structure of Collagen, Advan. Protein Chem.25, 243–352 (1971).

    Google Scholar 

  34. A.J. Bailey, S.P. Robins andG. Balian,Biological Significance of the Intermolecular Crosslinks of Collagen, Nature251, 105–109 (1974).

    Google Scholar 

  35. E.J. Miller,A Review of Biochemical Studies on the Genetically Distinct Collagens of the Skeletal System, Clin. Orthopaed.92, 260–280 (1973).

    Google Scholar 

  36. G. Balian andA.J. Bailey,Nature and Location of Crosslinks in Cartilage Collagen, Ann. Rheum. Dis.34, Suppl. 2, 41–42 (1975).

    Google Scholar 

  37. E.D. Harris, Jr. andS.M. Krane,Collagenases, New Eng. J. Med.291, 605–609 (1974).

    Google Scholar 

  38. E.D. Harris, Jr. andE. Cartwright,Mammalian Collagenases, in:Proteinases in Mammalian Cells and Tissues (Ed. A.J. Barrett; North-Holland Publ. Co., Amsterdam, 1977), pp. 249–283.

    Google Scholar 

  39. E.D. Harris, Jr. andM.E. Farrell,Resistance to Collagenase: a Characteristic of Collagen Fibrils Cross-Linked with Formaldehyde, Biochim. Biophys. Acta278, 133–141 (1972).

    Google Scholar 

  40. F.S. Steven,Observations on the Different Substrate Behaviour of Tropocollagen Molecules in Solution and Intermolecularly Cross-Linked Tropocollagen within Insoluble Polymeric Collagen Fibrils, Biochem. J.155, 391–400 (1976).

    Google Scholar 

  41. A. Janoff andJ. Blondin,Depletion of Cartilage Matrix by a Neutral Protease Fraction of Human Leucocyte Lysosomes, Proc. Soc. Exp. Biol. Med.135, 302–306 (1970).

    Google Scholar 

  42. M.C. Burleigh,Degradation of Collagen by Non-Specific Proteinases, in:Proteinases in Mammalian Cells and Tissues (Ed. A.J. Barrett; North-Holland Publ. Co., Amsterdam, 1977), pp. 285–309.

    Google Scholar 

  43. B. Hazleman, D.Y. Bulgen, J.T. Dingle andA.J. Barrett (in preparation).

  44. S. Ruddy,Synovial Fluid: Mirror of the Inflammatory Lesion in Rheumatoid Arthritis, in:Rheumatoid Arthritis (Ed. E.D. Harris, Jr; Medcom Press, New York, 1974), pp. 58–71.

    Google Scholar 

  45. K. Ohlsson andM. Delshammar,Interactions Between Granulocyte Elastase and the Plasma Proteinase Inhibitors in vitro and in vivo, in:Dynamics of Connective Tissue Macromolecules (Eds. P.M. Burleigh and A.R. Poole; North-Holland Publ. Co., Amsterdam, 1975), pp. 259–275.

    Google Scholar 

  46. K. Ohlsson andU. Åkesson, α1-Antichymotrypsin Interaction with Cationic Proteins from Granulocytes, Clin. Chim. Acta73, 285–291 (1976).

    Google Scholar 

  47. T.D. Cooke, E.R. Hurd, H.E. Jasin, M. Bienenstock andM. Ziff,Identification of Immunoglobulins and Complement in Rheumatoid Articular Collagenous Tissues, Arthritis Rheum.18, 541–551 (1975).

    Google Scholar 

  48. W. Martell,Radiology of the Rheumatic Diseases, in:Arthritis and Allied Conditions (Eds. J.L. Hollander and D.J. McCarty; Lea and Febiger, Philadelphia, 1974), pp. 82–135.

    Google Scholar 

  49. D. Hamerman,Cartilage Changes in the Rheumatoid Joint, Clin. Orthopaed.64, 91–97 (1969).

    Google Scholar 

  50. E.D. Harris, Jr.,The Proliferative Lesion in Rheumatoid Arthritis: Manifestations and Pathophysiology, in:Rheumatoid Arthritis (Ed. E.D. Harris, Jr.; Medcom Press, New York 1974), pp. 72–98.

    Google Scholar 

  51. H. Kimura, H. Tateishi andM. Ziff,Surface Ultrastructure of Rheumatoid Articular Cartilage, Arthritis Rheum. (1977) (in press).

  52. J.C. Powers,Inhibitors of Elastase and Pulmonary Emphysema, Trends Biochem. Sci.1, 211–214 (1976).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barrett, A.J. The possible role of neutrophil proteinases in damage to articular cartilage. Agents and Actions 8, 11–18 (1978). https://doi.org/10.1007/BF01972396

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01972396

Keywords

Navigation