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. 1989 Mar;83(3):876–882. doi: 10.1172/JCI113971

Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions.

W D Xu 1, G S Firestein 1, R Taetle 1, K Kaushansky 1, N J Zvaifler 1
PMCID: PMC303761  PMID: 2646320

Abstract

A liquid culture technique was used to study 23 synovial fluids (SF) (21 from inflammatory joint diseases and 2 noninflammatory SF) and supernatants of two cultured rheumatoid arthritis (RA) synovial tissues for colony-stimulating factor (CSF). The proliferative responses of human peripheral blood macrophage-depleted non-T cells treated with synovial fluids, supernatants of synovial tissue explants, and recombinant granulocyte-macrophage (rGM)-CSF were compared. Aggregates of cells that formed in long-term cultures (15 d) were similar for each applied agent and consisted of macrophages, eosinophils, and large blasts. Tritiated thymidine incorporation was proportional to the concentration of rGM-CSF and was accompanied by an increase in number and size of cellular aggregates formed in the cultures. CSF activity was observed in inflammatory SF, with tritiated thymidine uptake of 3,501 +/- 1,140 cpm in the presence of RA samples (n = 15) compared to 1,985 +/- 628 for non-RA inflammatory SF (n = 7) (P less than 0.05) and 583 +/- 525 for medium (n = 6) (P less than 0.01). The proliferative response to RA SF was often more apparent when the samples were diluted, because at higher concentrations the RA SF was inhibitory. Two RA SF were fractionated by Sephadex G100 column chromatography; low levels of CSF activity were detected in fractions corresponding to Mr of 70-100 kD, but the major CSF activity was found in the 20-24-kD fractions. A polyclonal rabbit anti-GM-CSF antibody eliminated the stimulating activity from both rGM-CSF and RA SF. Finally, a specific RIA identified significant levels of GM-CSF (40-140 U/ml) in the culture supernatants of 3 additional RA synovial tissues. These data document the local production of GM-CSF in rheumatoid synovitis and are the first description of this cytokine at a site of disease activity.

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Selected References

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  1. Denburg J. A., Telizyn S., Messner H., Lim B., Jamal N., Ackerman S. J., Gleich G. J., Bienenstock J. Heterogeneity of human peripheral blood eosinophil-type colonies: evidence for a common basophil-eosinophil progenitor. Blood. 1985 Aug;66(2):312–318. [PubMed] [Google Scholar]
  2. Firestein G. S., Tsai V., Zvaifler N. J. Cellular immunity in the joints of patients with rheumatoid arthritis and other forms of chronic synovitis. Rheum Dis Clin North Am. 1987 Aug;13(2):191–213. [PubMed] [Google Scholar]
  3. Firestein G. S., Xu W. D., Townsend K., Broide D., Alvaro-Gracia J., Glasebrook A., Zvaifler N. J. Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. J Exp Med. 1988 Nov 1;168(5):1573–1586. doi: 10.1084/jem.168.5.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Firestein G. S., Zvaifler N. J. Peripheral blood and synovial fluid monocyte activation in inflammatory arthritis. II. Low levels of synovial fluid and synovial tissue interferon suggest that gamma-interferon is not the primary macrophage activating factor. Arthritis Rheum. 1987 Aug;30(8):864–871. doi: 10.1002/art.1780300804. [DOI] [PubMed] [Google Scholar]
  5. Fleischmann J., Golde D. W., Weisbart R. H., Gasson J. C. Granulocyte-macrophage colony-stimulating factor enhances phagocytosis of bacteria by human neutrophils. Blood. 1986 Sep;68(3):708–711. [PubMed] [Google Scholar]
  6. Gasson J. C., Weisbart R. H., Kaufman S. E., Clark S. C., Hewick R. M., Wong G. G., Golde D. W. Purified human granulocyte-macrophage colony-stimulating factor: direct action on neutrophils. Science. 1984 Dec 14;226(4680):1339–1342. doi: 10.1126/science.6390681. [DOI] [PubMed] [Google Scholar]
  7. Griffin J. D., Sullivan R., Beveridge R. P., Larcom P., Schlossman S. F. Induction of proliferation of purified human myeloid progenitor cells: a rapid assay for granulocyte colony-stimulating factors. Blood. 1984 Apr;63(4):904–911. [PubMed] [Google Scholar]
  8. Husby G., Williams R. C., Jr Immunohistochemical studies of interleukin-2 and gamma-interferon in rheumatoid arthritis. Arthritis Rheum. 1985 Feb;28(2):174–181. doi: 10.1002/art.1780280212. [DOI] [PubMed] [Google Scholar]
  9. Kaushansky K., O'Hara P. J., Hart C. E., Forstrom J. W., Hagen F. S. Role of carbohydrate in the function of human granulocyte-macrophage colony-stimulating factor. Biochemistry. 1987 Jul 28;26(15):4861–4867. doi: 10.1021/bi00389a038. [DOI] [PubMed] [Google Scholar]
  10. Leary A. G., Ogawa M. Blast cell colony assay for umbilical cord blood and adult bone marrow progenitors. Blood. 1987 Mar;69(3):953–956. [PubMed] [Google Scholar]
  11. Lotz M., Tsoukas C. D., Robinson C. A., Dinarello C. A., Carson D. A., Vaughan J. H. Basis for defective responses of rheumatoid arthritis synovial fluid lymphocytes to anti-CD3 (T3) antibodies. J Clin Invest. 1986 Sep;78(3):713–721. doi: 10.1172/JCI112631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moore R. N., Oppenheim J. J., Farrar J. J., Carter C. S., Jr, Waheed A., Shadduck R. K. Production of lymphocyte-activating factor (Interleukin 1) by macrophages activated with colony-stimulating factors. J Immunol. 1980 Sep;125(3):1302–1305. [PubMed] [Google Scholar]
  13. Morrissey P. J., Bressler L., Park L. S., Alpert A., Gillis S. Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells. J Immunol. 1987 Aug 15;139(4):1113–1119. [PubMed] [Google Scholar]
  14. Quesenberry P. J., Gimbrone M. A., Jr Vascular endothelium as a regulator of granulopoiesis: production of colony-stimulating activity by cultured human endothelial cells. Blood. 1980 Dec;56(6):1060–1067. [PubMed] [Google Scholar]
  15. Ralph P., Broxmeyer H. E., Nakoinz I. Immunostimulators induce granulocyte/macrophage colony-stimulating activity and block proliferation in a monocyte tumor cell line. J Exp Med. 1977 Aug 1;146(2):611–616. doi: 10.1084/jem.146.2.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rhyner K., Taetle R. CSF-responsive bone marrow cells in liquid culture: characterization and screening applications. Int J Cell Cloning. 1986 Jan;4(1):27–42. doi: 10.1002/stem.5530040104. [DOI] [PubMed] [Google Scholar]
  17. Schlunk T., Schleyer M. The influence of culture conditions on the production of colony-stimulating activity by human placenta. Exp Hematol. 1980 Feb;8(2):179–184. [PubMed] [Google Scholar]
  18. Silberstein D. S., Owen W. F., Gasson J. C., DiPersio J. F., Golde D. W., Bina J. C., Soberman R., Austen K. F., David J. R. Enhancement of human eosinophil cytotoxicity and leukotriene synthesis by biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor. J Immunol. 1986 Nov 15;137(10):3290–3294. [PubMed] [Google Scholar]
  19. Sullivan R., Gans P. J., McCarroll L. A. The synthesis and secretion of granulocyte-monocyte colony-stimulating activity (CSA) by isolated human monocytes: kinetics of the response to bacterial endotoxin. J Immunol. 1983 Feb;130(2):800–807. [PubMed] [Google Scholar]
  20. Weisbart R. H., Golde D. W., Clark S. C., Wong G. G., Gasson J. C. Human granulocyte-macrophage colony-stimulating factor is a neutrophil activator. 1985 Mar 28-Apr 3Nature. 314(6009):361–363. doi: 10.1038/314361a0. [DOI] [PubMed] [Google Scholar]
  21. Zucali J. R., Dinarello C. A., Oblon D. J., Gross M. A., Anderson L., Weiner R. S. Interleukin 1 stimulates fibroblasts to produce granulocyte-macrophage colony-stimulating activity and prostaglandin E2. J Clin Invest. 1986 Jun;77(6):1857–1863. doi: 10.1172/JCI112512. [DOI] [PMC free article] [PubMed] [Google Scholar]

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