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. 1990 May;49(5):301–307. doi: 10.1136/ard.49.5.301

Concentrations of glycosaminoglycans in synovial fluids and their relation with immunological and inflammatory mediators in rheumatoid arthritis.

A Bensouyad 1, A P Hollander 1, B Dularay 1, A E Bedwell 1, R A Cooper 1, C W Hutton 1, P A Dieppe 1, C J Elson 1
PMCID: PMC1004073  PMID: 2344209

Abstract

The dimethylmethylene blue assay showed higher concentrations of glycosaminoglycans in many synovial fluids from patients with rheumatoid arthritis (RA) than in autologous sera or sera or synovial fluids from normal subjects. These results were taken to suggest that the glycosaminoglycans in RA synovial fluid were abnormally raised and derived from cartilage. To discover what stimulated such glycosaminoglycan release in RA joints relations were sought between synovial fluid concentrations of glycosaminoglycans and immunological and inflammatory mediators. It was shown that RA synovial fluid glycosaminoglycan concentrations correlated with synovial fluid C3d concentrations but not with synovial fluid rheumatoid factor concentrations, polymorphonuclear leucocyte numbers, myeloperoxidase concentrations, or the ability of the synovial fluids to release free radicals from normal polymorphonuclear leucocytes. A correlation was found between synovial fluid C3d and interleukin 1 concentrations as judged by both lymphocyte activating factor activity and immunoassay, but no significant correlation was detected between interleukin 1 and glycosaminoglycan concentrations. It is suggested that in the rheumatoid joint locally produced cytokines, in addition to interleukin 1, together stimulate glycosaminoglycan release from cartilage and render it vulnerable to attack by other processes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abdel-Nour A. N., Elson C. J., Dieppe P. A. Proliferative responses of T-cell lines grown from joint fluids of patients with rheumatoid arthritis and other arthritides. Immunol Lett. 1986 Jun;12(5-6):329–333. doi: 10.1016/0165-2478(86)90038-6. [DOI] [PubMed] [Google Scholar]
  2. Arend W. P., Joslin F. G., Massoni R. J. Effects of immune complexes on production by human monocytes of interleukin 1 or an interleukin 1 inhibitor. J Immunol. 1985 Jun;134(6):3868–3875. [PubMed] [Google Scholar]
  3. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  4. Babior B. M., Kipnes R. S., Curnutte J. T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744. doi: 10.1172/JCI107236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bedwell A. E., Elson C. J., Carter S. D., Dieppe P. A., Hutton C. W., Czudek R. Isolation and analysis of complement activating aggregates from synovial fluid of patients with rheumatoid arthritis using monoclonal anti-C3d antibodies. Ann Rheum Dis. 1987 Jan;46(1):55–64. doi: 10.1136/ard.46.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bertolini D. R., Nedwin G. E., Bringman T. S., Smith D. D., Mundy G. R. Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature. 1986 Feb 6;319(6053):516–518. doi: 10.1038/319516a0. [DOI] [PubMed] [Google Scholar]
  7. Brandslund I., Siersted H. C., Svehag S. E., Teisner B. Double-decker rocket immunoelectrophoresis for direct quantitation of complement C3 split products with C3d specificities in plasma. J Immunol Methods. 1981;44(1):63–71. doi: 10.1016/0022-1759(81)90107-1. [DOI] [PubMed] [Google Scholar]
  8. Burkhardt H., Schwingel M., Menninger H., Macartney H. W., Tschesche H. Oxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes. Arthritis Rheum. 1986 Mar;29(3):379–387. doi: 10.1002/art.1780290311. [DOI] [PubMed] [Google Scholar]
  9. Carroll G. J. Spectrophotometric measurement of proteoglycans in osteoarthritic synovial fluid. Ann Rheum Dis. 1987 May;46(5):375–379. doi: 10.1136/ard.46.5.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dingle J. T., Page Thomas D. P., Hazleman B. The role of cytokines in arthritic diseases: in vitro and in vivo measurements of cartilage degradation. Int J Tissue React. 1987;9(4):349–354. [PubMed] [Google Scholar]
  11. Duke O., Panayi G. S., Janossy G., Poulter L. W. An immunohistological analysis of lymphocyte subpopulations and their microenvironment in the synovial membranes of patients with rheumatoid arthritis using monoclonal antibodies. Clin Exp Immunol. 1982 Jul;49(1):22–30. [PMC free article] [PubMed] [Google Scholar]
  12. Dularay B., Elson C. J., Dieppe P. A. Enhanced oxidative response of polymorphonuclear leukocytes from synovial fluids of patients with rheumatoid arthritis. Autoimmunity. 1988;1(3):159–169. doi: 10.3109/08916938808997161. [DOI] [PubMed] [Google Scholar]
  13. Elson C. J., Scott D. G., Blake D. R., Bacon P. A., Holt P. D. Complement-activating rheumatoid-factor-containing complexes in patients with rheumatoid vasculitis. Ann Rheum Dis. 1983 Apr;42(2):147–150. doi: 10.1136/ard.42.2.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Farndale R. W., Buttle D. J., Barrett A. J. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta. 1986 Sep 4;883(2):173–177. doi: 10.1016/0304-4165(86)90306-5. [DOI] [PubMed] [Google Scholar]
  15. Farndale R. W., Sayers C. A., Barrett A. J. A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. Connect Tissue Res. 1982;9(4):247–248. doi: 10.3109/03008208209160269. [DOI] [PubMed] [Google Scholar]
  16. Fell H. B., Jubb R. W. The effect of synovial tissue on the breakdown of articular cartilage in organ culture. Arthritis Rheum. 1977 Sep-Oct;20(7):1359–1371. doi: 10.1002/art.1780200710. [DOI] [PubMed] [Google Scholar]
  17. Gery I., Gershon R. K., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972 Jul 1;136(1):128–142. doi: 10.1084/jem.136.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Goodman M. G., Chenoweth D. E., Weigle W. O. Induction of interleukin 1 secretion and enhancement of humoral immunity by binding of human C5a to macrophage surface C5a receptors. J Exp Med. 1982 Sep 1;156(3):912–917. doi: 10.1084/jem.156.3.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hadler N. M., Spitznagel J. K., Quinet R. J. Lysosomal enzymes in inflammatory synovial effusions. J Immunol. 1979 Aug;123(2):572–577. [PubMed] [Google Scholar]
  20. Hardingham T., Burditt L., Ratcliffe A. Studies on the synthesis, secretion and assembly of proteoglycan aggregates by chondrocytes. Prog Clin Biol Res. 1984;151:17–29. [PubMed] [Google Scholar]
  21. Holt P. D., Donaldson C., Judson P. A., Johnson P., Parsons S. F., Anstee D. J. NBTS/BRIC 8. A monoclonal anti-C3d antibody. Transfusion. 1985 May-Jun;25(3):267–269. doi: 10.1046/j.1537-2995.1985.25385219912.x. [DOI] [PubMed] [Google Scholar]
  22. Horowitz M., Vignery A., Gershon R. K., Baron R. Thymus-derived lymphocytes and their interactions with macrophages are required for the production of osteoclast-activating factor in the mouse. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2181–2185. doi: 10.1073/pnas.81.7.2181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kurosaka M., Ziff M. Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium. J Exp Med. 1983 Oct 1;158(4):1191–1210. doi: 10.1084/jem.158.4.1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lunec J., Halloran S. P., White A. G., Dormandy T. L. Free-radical oxidation (peroxidation) products in serum and synovial fluid in rheumatoid arthritis. J Rheumatol. 1981 Mar-Apr;8(2):233–245. [PubMed] [Google Scholar]
  25. Page-Thomas D. P., Bard D., King B., Dingle J. T. Clearance of proteoglycan from joint cavities. Ann Rheum Dis. 1987 Dec;46(12):934–937. doi: 10.1136/ard.46.12.934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pettipher E. R., Higgs G. A., Henderson B. Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8749–8753. doi: 10.1073/pnas.83.22.8749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pugh D., Etherington D. J., Silver I. A. Acid hydrolase distribution in sensitised and naive macrophages in vivo and in vitro. Z Mikrosk Anat Forsch. 1984;98(3):375–384. [PubMed] [Google Scholar]
  28. Rifas L., Shen V., Mitchell K., Peck W. A. Macrophage-derived growth factor for osteoblast-like cells and chondrocytes. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4558–4562. doi: 10.1073/pnas.81.14.4558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Saklatvala J., Pilsworth L. M., Sarsfield S. J., Gavrilovic J., Heath J. K. Pig catabolin is a form of interleukin 1. Cartilage and bone resorb, fibroblasts make prostaglandin and collagenase, and thymocyte proliferation is augmented in response to one protein. Biochem J. 1984 Dec 1;224(2):461–466. doi: 10.1042/bj2240461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature. 1986 Aug 7;322(6079):547–549. doi: 10.1038/322547a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sandy J. D., Sriratana A., Brown H. L., Lowther D. A. Evidence for polymorphonuclear-leucocyte-derived proteinases in arthritic cartilage. Biochem J. 1981 Jan 1;193(1):193–202. doi: 10.1042/bj1930193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Suzuki K., Ota H., Sasagawa S., Sakatani T., Fujikura T. Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal Biochem. 1983 Jul 15;132(2):345–352. doi: 10.1016/0003-2697(83)90019-2. [DOI] [PubMed] [Google Scholar]
  33. Winchester R. J., Agnello V., Kunkel H. G. Gamma globulin complexes in synovial fluids of patients with rheumatoid arthritis. Partial characterization and relationship to lowered complement levels. Clin Exp Immunol. 1970 May;6(5):689–706. [PMC free article] [PubMed] [Google Scholar]
  34. Zvaifler N. J. Breakdown products of C 3 in human synovial fluids. J Clin Invest. 1969 Aug;48(8):1532–1542. doi: 10.1172/JCI106119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. van Eden W., Holoshitz J., Nevo Z., Frenkel A., Klajman A., Cohen I. R. Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5117–5120. doi: 10.1073/pnas.82.15.5117. [DOI] [PMC free article] [PubMed] [Google Scholar]

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