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Thrombin and fibrin-induced growth of fibroblasts: Role in wound repair and thrombus organization

Steigerung der Fibroblastenproliferation durch Thrombin und Fibrin in vitro und ihre Rolle bei Wundheilung und Thrombusorganisation

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Zusammenfassung

Fibroblastenkulturen wurden während der logarithmischen Wachstumsphase mit verschiedenen Komponenten des Gerinnungssystems (Thrombin, Fibrinogen, Fibrin) behandelt. Die Beeinflussung der proliferativen Aktivität der Fibroblasten erfolgte durch Messung der3H-TdR-Einbaurate sowie durch Zellzählung. Fibrin und Thrombin zeigten eine konzentrationsabhängige Steigerung des Zellwachstums. Fibrinogen in verschiedenen Konzentrationen war ohne Effekt. Durch Züchtung von Fibroblasten in polymerisierendem, mit Nährmedium angereichtertem Fibrin entstanden elongierte, sich im Gerinnsel netzförmig ausbreitende Zellverbände. Die Zellen vermehrten sich um das Achtfache, nach etwa 10tägiger Kulturdauer sistierte das Zellwachstum infolge nutritiver Deprivation. Die Ergebnisse zeigen, daß Fibroblasten sich in Fibringerinnseln ausbreiten und vermehren. Thrombin bewirkt neben der Fibrinogen-Fibrin-Conversion eine anhaltende Steigerung der Fibroblastenproliferation, die bei der Wundheilung, der Organisation von Thromben und der Ausbildung atheromatöser Veränderungen von Bedeutung zu sein scheint.

Summary

Skin fibroblast cultures were treated with various components of the blood clotting system (thrombin, fibrinogen and fibrin) during the logarithmic growth phase. Fibrin as well as thrombin showed dose-dependent growth promoting activities as revealed by cell counting and3H-thymidine uptake. No effect was seen with fibrinogen. After entrapping in polymerizing fibrin enriched by complete culture medium the cells elongated, multiplied and formed net-like interconnecting cell strands throughout the clots. Nutritional deprivation appeared as a limiting factor for eventual growth cessation. The results demonstrate active growth of fibroblasts in fibrin clots such as present in healing wounds and thrombi. The production of thrombin by the coagulation cascade does not only result in the conversion of fibrinogen to fibrin but has also a long-lasting hormone-like effect on fibroblast proliferation which is of essential importance in wound healing, thrombus organization and progression of chronic atherosclerotic lesions.

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References

  • Abercrombie, M., Heaysman, J.E.M.: Observations on the social behaviour of cells in tissue culture. II. “Monolayering” of fibroblasts. Exp. Cell Res.6, 293 (1954)

    Google Scholar 

  • Abercrombie, M., Ambrose, E.J.: Interference microscopie studies of cell contacts in tissue culture. Exp. Cell Res.15, 332 (1958)

    Google Scholar 

  • Banerjee, S.K., Glynn, L.E.: Reactions to homologous and heretologous fibrin implants in experimental animals. Ann. N.Y. Acad. Sci.86, 1054 (1960)

    Google Scholar 

  • Beneke, G.: Der Thrombus als pathologisch-anatomisches Substrat. Therapeutische und experimentelle Fibrinolyse. Hiemeyer, V. (ed.), Stuttgart: F.K. Schattauer 1969

    Google Scholar 

  • Chen, L.B., Buchanan, J.M.: Mitogenic activity of blood components. I. Thrombin and prothrombin. Proc. Nat. Acad. Sci. USA72, 131 (1975)

    Google Scholar 

  • Chen, L.B., Teng, N.N.H., Buchanan, J.M.: The mitogenic activity and related effects of thrombin on chick embryo fibroblasts. Proteases and biological control. Cold spring harbor conf. cell proliferat.2, 957 (1975)

    Google Scholar 

  • Dulbecco, R., Elkington, J.: Conditions limiting multiplication of fibroblastic and epithelial cells in dense cultures. Nature246, 197 (1973)

    Google Scholar 

  • Hassel, J., Engelhard, D.L.: Factors regulating the multiplication of animal cells in culture. Exp. Cell Res.107, 159 (1977)

    Google Scholar 

  • Heene, D.L.: Zur Biochemie des Prothrombins. In: Biochemie und Aktivierung des Prothrombins, Schroer, H. (Hrsg.). S. 3. Stuttgart: F.K. Schattauer 1968

    Google Scholar 

  • McCoy, L.E., Waler, D.A., Seegers, W.H.: Purchication and Biochemistry of Thrombin. In: Physiology and Biochemistry of Prothrombin conversion. Mammary, E.F., Anderson, G.F., Bornhart, M.I. (eds.). p. 125. Stuttgart-New York: F.K. Schattauer 1974

    Google Scholar 

  • Niewiarowski, S., Regoeczi, E., Mustard, J.F.: Adhesion of fibroblasts to polymerizing fibrin and retraction of fibrin induced by fibroblasts. Proc. Soc. Exp. Biol. Med.140, 199 (1972)

    Google Scholar 

  • Nozawa, R.T.: Altered morphology and increased cell adhesiveness of chinese hamster ovary cells cultured on fibrin. J. Cell Physiol.90, 351 (1977)

    Google Scholar 

  • Pearlstein, E.: Plasma membrane glycoprotein which mediates adhesion of fibroblasts to collagen. Nature262, 497 (1976)

    Google Scholar 

  • Pojanpelto, P.: Proteases stimulate proliferation of human fibroblasts. J. Cell. Physiol.91, 351 (1977)

    Google Scholar 

  • Rein, A., Rubin, H.: Effects of local cell concentration upon the growth of chick embryo cells in tissue culture. Exp. Cell Res.49, 666 (1968)

    Google Scholar 

  • Schwick, H.G., Trobisch, H., Heimburger, N.: Leistungsfähigkeit und Grenzen immunologischer Methoden in der Gerinnungsdiagnostik. Internist14, 4, 160 (1973)

    Google Scholar 

  • Stoker, M.G.P., Rubin, H.: Sensity dependent inhibition of cell growth in culture. Nature215, 171 (1967)

    Google Scholar 

  • Teng, N.N.H., Chen, L.B.: The role of surface proteins in cell proliferations as studied with thrombin and other proteases. Proc. Nat. Med. Sci. USA72, 413 (1975)

    Google Scholar 

  • Zetter, B.R., Sun, T.-T., Chen, L.B., Buchanan, J.M.: Thrombin potentiates the mitogenic response of cultured fibroblasts to serum and other growth promoting agents. J. Cell. Physiol.92, 233 (1977)

    Google Scholar 

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Pohl, J., Bruhn, H.D. & Christophers, E. Thrombin and fibrin-induced growth of fibroblasts: Role in wound repair and thrombus organization. Klin Wochenschr 57, 273–277 (1979). https://doi.org/10.1007/BF01476508

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