The Role of Cytokines in the Symbiotic Relationship between Leukocytes and Vascular Endothelia

  • Alberto Mantovani
  • Elisabetta Dejana


Inflammatory reactions and immunity involve close interactions between immunocompetent cells and the vessel wall (Baldwin, 1982). The extravasation and localization at inflammatory sites of leukocytes involve adhesion to and passage through endothelial linings. Changes in the vessel wall, including vasodilation and proliferation of capillary endothelial cells are well documented at sites of cell-mediated immune reactions involving leukocyte recruitment. In recent years, we and others have accumulated evidence indicating that inflammatory lymphokines released by leukocytes play a pivotal role in the interaction between vascular cells and circulating white blood cells. Soluble products released by lymphocytes and macrophages are potent regulators of various functions of vascular cells, such as proliferation, migration, production of colony stimulating factors and expression of class II (Ia) histocompatibility antigens. The molecules which mediate the symbiotic relationship of leukocytes with vascular cells have been, to some extent, defined recently. Thus interferon-γ (IFN-γ) has been shown to regulate the expression of Ia antigens in various cells including vascular endothelium (Pober et al., 1983). More recently, the mononuclear phagocyte products interleukin-1 (IL-1) and tumor necrosis factor (TNF) have been shown to profoundly affect the functional competence of vessel wall cells. IL-1 and TNF are released by mononuclear phagocytes following activation, and these monokines are likely to play a crucial role in various pathological conditions, including inflammatory reactions and endotoxin shock (for review Dinarello, 1985; Old, 1985).


Tumor Necrosis Factor Vascular Endothelium Human Endothelial Cell Mononuclear Phagocyte Procoagulant Activity 
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  1. Baldwin, W.M. III. The symbiosis of immunocompetent and endothelial cells. Immunol. Today 3:267–269, 1982.CrossRefGoogle Scholar
  2. Bevilacqua, M.P., Pober, J.S., Majeau, G.R., Contran, R.S. and Gimbrone, M.A. Jr. Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J. Exp. Med. 160:618–623, 1984.PubMedCrossRefGoogle Scholar
  3. Bevilacqua, M.P., Pober, J.S., Majeau, G.R., Fiers, W., Cotran, R.S. and Gimbrone, M.A. Jr. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: Characterization and comparison with the actions of interleukin 1. Proc. Natl. Acad. Sci. USA 83:4533–4537, 1986.PubMedCrossRefGoogle Scholar
  4. Bevilacqua, M.P., Pober, J.S., Wheeler, M.E., Cotran, R.S. and Gimbrone, M.A. Jr. Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J. Clin. Invest. 76:2003–2007, 1985PubMedCrossRefGoogle Scholar
  5. Bussolino, F., Breviario, F., Tetta, C., Aglietta, M., Mantovani, A. and Dejana, E. Interleukin 1 stimulates platelet-activating factor production in cultured human endothelial cells. J. Clin. Inves. 77:2027–2033, 1986.CrossRefGoogle Scholar
  6. Colotta, F., Lampugnani, M.G., Polentarutti, N., Dejana, E. and Mantovani, A. Interleukin-1 induces c-fos protooncogene expression in cultured human endothelial cells. Biochem. Biophys. Res. Commun. 152:1106–1110, 1988.CrossRefGoogle Scholar
  7. Colotta, F., Wang, J.M., Polentarutti, N. and Mantovani, A. Expression of c-fos protooncogene in normal human peripheral blood granulocytes. J. Exp. Med 165:1224–1229, 1987.PubMedCrossRefGoogle Scholar
  8. Dejana, E., Breviario, F., Balconi, G., Rossi, V., Remuzzi, G., de Gaetano, G. and Mantovani, A. Stimulation of prostacyclin synthesis in vascular cells by mononuclear cell products. Blood 64: 1280–1283, 1984.PubMedGoogle Scholar
  9. Dinarello, C.A. An update on human interleukin-1: From molecular biology to clinical relevance. J. Clin. Immunol. 5287–5298, 1985.Google Scholar
  10. Emeis, J.J. and Kooistra, T. Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. J. Exp. Med 163:1260–1266, 1986.PubMedCrossRefGoogle Scholar
  11. Gramse, M., Breviario, F., Pintucci, G., Millet, I., Dejana, E., Van Damme, J., Donati, M.B. and Mussoni, L. Enhancement by interleukin-1 of plasminogen activator inhibitor (PA-I) activity in cultured human endothelial cells. Biochem. Biophys. Res. Commun. 139:720–725, 1986.CrossRefGoogle Scholar
  12. Introna, M., Hamilton, T.A., Kaufman, R.E., Adams, D.O. and Bast, R.C. Jr. Treatment of murine peritoneal macrophages with bacterial lipopolysaccharide alters expression of c-fos and c-myc oncogenes. J. Immunol. 137:2711–2720, 1986.PubMedGoogle Scholar
  13. Kawakami, M., Ishibashi, S., Ogawa, H., Murase, T., Takaku, F. and Shibata, S. Cachectin/-TNF as well as interleukin-1 induces prostacyclin syndesis in cultured vascular endothelial cells. Biochem. Biophys. Res. Commun. 141:482–487, 1986.PubMedCrossRefGoogle Scholar
  14. Mantovani, A. and Dejana, E. Modulation of endothelial function by interleukin-1. A novel target for pharmacological intervention? Biochem. Pharmacol. 36:301–305, 1987PubMedCrossRefGoogle Scholar
  15. Old, L.J. Tumor necrosis factor (TNF). Science 230:630–634, 1985.PubMedCrossRefGoogle Scholar
  16. Pober, J.S., Bevilacqua, M.P., Mendrick, D.L., Lapierre, L.A., Fiers, W. and Gimbrone, M.A. Jr. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J.Immunol. 136:1680–1688, 1986.PubMedGoogle Scholar
  17. Pober, J.S., Gimbrone, M.A. Jr, Cotran, R.S., Reiss, C.S., Burakoff, S.J., Fiers, W. and Ault, K.A. Ia expression by vascular endothelium is inducible by activated T cells and by human gamma-interferon. J. Exp. Med 157:1339–1353, 1983.PubMedCrossRefGoogle Scholar
  18. Rossi, V., Breviario, F., Ghezzi, P., Dejana, E. and Mantovani, A. Prostacyclin synthesis induced in vascular cells by interleukin-1. Science 229:174–176, 1985.PubMedCrossRefGoogle Scholar
  19. Van Damme, J., Opdenakker, G., Simpson, R.J., Rubira, M.R., Cayphas, S., Vink, A., Billiau, A and Van Snick, J. Identification of the human 26-kD protein, interferon β 2(IFN-β 2, as a B cell hybridoma/plasmocytoma growth factor induced by interleukin 1 and tumor necrosis factor.J. Exp. Med. 165:914–925, 1987.PubMedCrossRefGoogle Scholar
  20. Wang, J.M., Bersani, L. and Mantovani, A. Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leukocytes. J. Immunol. 138:1469–1476, 1987.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Alberto Mantovani
    • 1
  • Elisabetta Dejana
    • 1
  1. 1.Istituto di Ricerche Farmacologiche “Mario Negri”MilanItaly

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