Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Jan 1;157(1):47–59. doi: 10.1084/jem.157.1.47

Alterations in collagen production in mixed mononuclear leukocyte- fibroblast cultures

PMCID: PMC2186892  PMID: 6549655

Abstract

The cell-cell interactions between fibroblasts and mononuclear leukocytes (MNL) which promote alterations in collagen accumulation were examined using a system of co-culture of human fibroblasts and peripheral blood MNL. The stimulation of collagen production was optimal after 48 h of co-culture and the increase in collagen correlated directly with the number of MNL added. The enhancement of collagen production was seen in both autologous and allogeneic co- cultures. Stimulation of non-collagenous protein was also noted. Co- culture supernatants contained soluble substances that were capable of stimulating collagen production, although they stimulated collagen production to a lesser degree than direct co-culture. Fractionation of these supernatants on Sephadex G-200 revealed a predominant area of stimulatory activity at 160,000 mol wt. Lesser areas of activity were noted at molecular weights of 80,000 and 25,000. Determination of the types of collagen produced by fibroblasts during co-culture with MNL showed that the ratio of type I:III collagen was decreased. These alterations in both the quantitative and qualitative accumulation of collagen mimic the changes often seen in wound healing and early inflammation suggesting that cellular interactions between fibroblasts and MNL may be important in the modulation of collagen production in normal and pathologic states.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Bailey A. J., Sims T. J., Le Lous, bazin S. Collagen polymorphism in experimental granulation tissue. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1160–1165. doi: 10.1016/0006-291x(75)90480-5. [DOI] [PubMed] [Google Scholar]
  2. Barnes M. J., Morton L. F., Bennett R. C., Bailey A. J., Sims T. J. Presence of type III collagen in guinea-pig dermal scar. Biochem J. 1976 Jul 1;157(1):263–266. doi: 10.1042/bj1570263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bienkowski R. S., Baum B. J., Crystal R. G. Fibroblasts degrade newly synthesised collagen within the cell before secretion. Nature. 1978 Nov 23;276(5686):413–416. doi: 10.1038/276413a0. [DOI] [PubMed] [Google Scholar]
  4. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  5. Bornstein P., Sage H. Structurally distinct collagen types. Annu Rev Biochem. 1980;49:957–1003. doi: 10.1146/annurev.bi.49.070180.004521. [DOI] [PubMed] [Google Scholar]
  6. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  7. Gadek J. E., Fells G. A., Wright D. G., Crystal R. G. Human neutrophil elastase functions as a type III collagen "collagenase". Biochem Biophys Res Commun. 1980 Aug 29;95(4):1815–1822. doi: 10.1016/s0006-291x(80)80110-0. [DOI] [PubMed] [Google Scholar]
  8. Gay R. E., Buckingham R. B., Prince R. K., Gay S., Rodnan G. P., Miller E. J. Collagen types synthesized in dermal fibroblast cultures from patients with early progressive systemic sclerosis. Arthritis Rheum. 1980 Feb;23(2):190–196. doi: 10.1002/art.1780230209. [DOI] [PubMed] [Google Scholar]
  9. Horwitz A. L., Hance A. J., Crystal R. G. Granulocyte collagenase: selective digestion of type I relative to type III collagen. Proc Natl Acad Sci U S A. 1977 Mar;74(3):897–901. doi: 10.1073/pnas.74.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Johnson R. L., Ziff M. Lymphokine stimulation of collagen accumulation. J Clin Invest. 1976 Jul;58(1):240–252. doi: 10.1172/JCI108455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Korn J. H. Modulation of lymphocyte mitogen responses by cocultured fibroblasts. Cell Immunol. 1981 Sep 15;63(2):374–384. doi: 10.1016/0008-8749(81)90016-2. [DOI] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Laskey R. A., Mills A. D. Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem. 1975 Aug 15;56(2):335–341. doi: 10.1111/j.1432-1033.1975.tb02238.x. [DOI] [PubMed] [Google Scholar]
  14. Mainardi C. L., Hasty D. L., Seyer J. M., Kang A. H. Specific cleavage of human type III collagen by human polymorphonuclear leukocyte elastase. J Biol Chem. 1980 Dec 25;255(24):12006–12010. [PubMed] [Google Scholar]
  15. Neilson E. G., Jimenez S. A., Phillips S. M. Cell-mediated immunity in interstitial nephritis. III. T lymphocyte-mediated fibroblast proliferation and collagen synthesis: an immune mechanism for renal fibrogenesis. J Immunol. 1980 Oct;125(4):1708–1714. [PubMed] [Google Scholar]
  16. Peterkofsky B., Diegelmann R. Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins. Biochemistry. 1971 Mar 16;10(6):988–994. doi: 10.1021/bi00782a009. [DOI] [PubMed] [Google Scholar]
  17. Seyer J. M., Hutcheson E. T., Kang A. H. Collagen polymorphism in idiopathic chronic pulmonary fibrosis. J Clin Invest. 1976 Jun;57(6):1498–1507. doi: 10.1172/JCI108420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Seyer J. M., Hutcheson E. T., Kang A. H. Collagen polymorphism in normal and cirrhotic human liver. J Clin Invest. 1977 Feb;59(2):241–248. doi: 10.1172/JCI108634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sporn M. B., Harris E. D., Jr Proliferative diseases. Am J Med. 1981 Jun;70(6):1231–1235. doi: 10.1016/0002-9343(81)90832-9. [DOI] [PubMed] [Google Scholar]
  20. Sykes B., Puddle B., Francis M., Smith R. The estimation of two collagens from human dermis by interrupted gel electrophoresis. Biochem Biophys Res Commun. 1976 Oct 18;72(4):1472–1480. doi: 10.1016/s0006-291x(76)80180-5. [DOI] [PubMed] [Google Scholar]
  21. Wahl S. M., Wahl L. M., McCarthy J. B. Lymphocyte-mediated activation of fibroblast proliferation and collagen production. J Immunol. 1978 Sep;121(3):942–946. [PubMed] [Google Scholar]
  22. Weiss J. B., Shuttleworth C. A., Brown R., Sedowfia K., Baildam A., Hunter J. A. Occurrence of type III collagen in inflamed synovial membranes: a comparison between non rheumatoid, rheumatoid, and normal synovial collagens. Biochem Biophys Res Commun. 1975 Aug 4;65(3):907–912. doi: 10.1016/s0006-291x(75)80471-2. [DOI] [PubMed] [Google Scholar]
  23. Welgus H. G., Jeffrey J. J., Eisen A. Z. The collagen substrate specificity of human skin fibroblast collagenase. J Biol Chem. 1981 Sep 25;256(18):9511–9515. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES