Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1979 Dec 1;150(6):1421–1431. doi: 10.1084/jem.150.6.1421

Inhibition of collagen synthesis by mononuclear cell supernates

PMCID: PMC2185728  PMID: 229188

Abstract

Mononuclear cell infiltration and alteration in the connective tissues are prominent features of the inflammatory response in a number of diseases. To determine whether mononuclear cell products can modulate collagen synthesis, human peripheral mononuclear cells from normal donors were isolated by Ficoll-Hypaque gradient centrifugation and then incubated for 48 h with or without phytohemagglutinin. Confluent cultures of normal, human skin fibroblasts were incubated with [14C]proline and various amounts of dialyzed supernates from the mononuclear cell cultures. Labeled, newly synthesized collagen was estimated by [14C]hydroxyproline analysis, collagenase digestion, and chromatography on Agarose A-5m in sodium dodecyl sulfate. The total incorporation of [14C]proline was not significantly affected by addition of the mononuclear cell supernates, but as much as 90% decrease in the synthesis by the fibroblasts of labeled collagen was found relative to controls. Supernates from the phytohemagglutinin- stimulated cultures were more active than those from nonstimulated cells. These results suggest that mononuclear cells can synthesize a factor(s) which can selectively inhibit collagen synthesis.

Full Text

The Full Text of this article is available as a PDF (669.4 KB).

Selected References

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

  1. Aalto M., Potila M., Kulonen E. The effect of silica-treated macrophages on the synthesis of collagen and other proteins in vitro. Exp Cell Res. 1976 Jan;97:193–202. doi: 10.1016/0014-4827(76)90668-6. [DOI] [PubMed] [Google Scholar]
  2. Bashey R. I., Jimenez S. A. Increased sensitivity of scleroderma fibroblasts in culture to stimulation of protein and collagen synthesis by serum. Biochem Biophys Res Commun. 1977 Jun 20;76(4):1214–1222. doi: 10.1016/0006-291x(77)90985-8. [DOI] [PubMed] [Google Scholar]
  3. Bańkowski E., Mitchell W. M. Human procollagen I. An anionic tropocollagen precursor from skin fibroblasts in culture. Biophys Chem. 1973 Dec;1(2):73–86. doi: 10.1016/0301-4622(73)80003-1. [DOI] [PubMed] [Google Scholar]
  4. Blanck T. J., Peterkofsky B. The stimulation of collagen secretion by ascorbate as a result of increased proline hydroxylation in chick embryo fibroblasts. Arch Biochem Biophys. 1975 Nov;171(1):259–267. doi: 10.1016/0003-9861(75)90031-4. [DOI] [PubMed] [Google Scholar]
  5. Burke J. M., Ross R. Collagen synthesis by monkey arterial smooth muscle cells during proliferation and quiescence in culture. Exp Cell Res. 1977 Jul;107(2):387–395. doi: 10.1016/0014-4827(77)90360-3. [DOI] [PubMed] [Google Scholar]
  6. Böyum A. Isolation of leucocytes from human blood. Further observations. Methylcellulose, dextran, and ficoll as erythrocyteaggregating agents. Scand J Clin Lab Invest Suppl. 1968;97:31–50. [PubMed] [Google Scholar]
  7. Carrel A. GROWTH-PROMOTING FUNCTION OF LEUCOCYTES. J Exp Med. 1922 Sep 30;36(4):385–391. doi: 10.1084/jem.36.4.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen L. B., Buchanan J. M. Mitogenic activity of blood components. I. Thrombin and prothrombin. Proc Natl Acad Sci U S A. 1975 Jan;72(1):131–135. doi: 10.1073/pnas.72.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feng J., Melcher A. H., Brunette D. M., Moe H. K. Determination of L-ascorbic acid levels in culture medium: concentrations in commercial media and maintenance of levels under conditions of organ culture. In Vitro. 1977 Feb;13(2):91–99. doi: 10.1007/BF02615072. [DOI] [PubMed] [Google Scholar]
  10. Gospodarowicz D., Moran J. S. Growth factors in mammalian cell culture. Annu Rev Biochem. 1976;45:531–558. doi: 10.1146/annurev.bi.45.070176.002531. [DOI] [PubMed] [Google Scholar]
  11. Heppleston A. G., Styles J. A. Activity of a macrophage factor in collagen formation by silica. Nature. 1967 Apr 29;214(5087):521–522. doi: 10.1038/214521a0. [DOI] [PubMed] [Google Scholar]
  12. Jimenez S. A., Bashey R. I. Collagen synthesis by scleroderma fibroblasts in culture. Arthritis Rheum. 1977 Apr;20(3):902–903. doi: 10.1002/art.1780200323. [DOI] [PubMed] [Google Scholar]
  13. Jimenez S. A., Dehm P., Prockop D. J. Further evidence for a transport form of collagen. Its extrusion and extracellular conversion to tropocollagen in embryonic tendon. FEBS Lett. 1971 Oct 1;17(2):245–248. doi: 10.1016/0014-5793(71)80156-4. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Juva K., Prockop D. J. Modified procedure for the assay of H-3-or C-14-labeled hydroxyproline. Anal Biochem. 1966 Apr;15(1):77–83. doi: 10.1016/0003-2697(66)90249-1. [DOI] [PubMed] [Google Scholar]
  16. Miyoshi M., Rosenbloom J. General proteolytic activity of highly purified preparations of clostridial collagenase. Connect Tissue Res. 1974;2(2):77–84. doi: 10.3109/03008207409152091. [DOI] [PubMed] [Google Scholar]
  17. Narayanan A. S., Page R. C. Serum modulates collagen types in human gingiva fibroblasts. FEBS Lett. 1977 Aug 1;80(1):221–224. doi: 10.1016/0014-5793(77)80444-4. [DOI] [PubMed] [Google Scholar]
  18. Nolan J. C., Cardinale G. J., Undenfriend S. The formation of hydroxyproline in collagen by cells grown in the absence of serum. Biochim Biophys Acta. 1978 Sep 21;543(1):116–122. doi: 10.1016/0304-4165(78)90459-2. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Wiebel F., Baserga R. Early alterations in amino acid pools and protein synthesis of diploid fibroblasts stimulated to synthesize DNA by addition of serum. J Cell Physiol. 1969 Oct;74(2):191–202. doi: 10.1002/jcp.1040740211. [DOI] [PubMed] [Google Scholar]

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

RESOURCES