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The possible role of neutrophil proteinases in damage to articular cartilage

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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.

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References

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

    PubMed  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).

    PubMed  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).

    Article  PubMed  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).

    Article  PubMed  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).

    PubMed  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).

    PubMed  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).

    PubMed  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).

    PubMed  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).

    Article  PubMed  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).

    PubMed  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).

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  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).

    PubMed  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).

    PubMed  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).

    PubMed  Google Scholar 

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

    Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  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).

    PubMed  Google Scholar 

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

    PubMed  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 Collage Fibrils, Biochim. Biophys. Acta405, 188–200 (1975).

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  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).

    PubMed  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).

    PubMed  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).

    PubMed  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).

    PubMed  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).

    PubMed  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. Hazileman, 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,α 1-Antichymotrypsin Interaction with Cationie Proteins from Granuloeytes, Clin. Chim. Acta73, 285–291 (1976).

    Article  PubMed  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).

    PubMed  Google Scholar 

  48. W. Martell,Radiology of the Rheumatic Diseases, in:Arthritis and Alled 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 Joing, 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 

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  1. Molecular Pathology Department, Strangeways Research Laboratory, CB1 4RN, Cambridge, England

    Alan J. Barrett

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Barrett, A.J. The possible role of neutrophil proteinases in damage to articular cartilage. Agents and Actions 43, 194–201 (1994). https://doi.org/10.1007/BF01986688

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