Skip to main content
SpringerLink
Log in

Endothelial Activation

Its Role in Inflammatory and Immune Reactions

  • Chapter
Endothelial Cell Biology in Health and Disease

Abstract

It has long been known that endothelium of postcapillary venules involved in the inflammatory response of a delayed-type hypersensitivity and other cell-mediated immune reactions, undergoes a number of functional and morphological alterations (Table 1).19’47 57 58 In particular, the vessels become hyperpermeable to macromolecules, and the endothelial cells undergo hypertrophy, acquire a plump cuboidal appearance, protrude into the lumen, and display increased biosynthetic organelles on electron microscopy. These changes have been described collectively as “endothelial activation,” and the cells themselves likened to the high endothelial venules of lymph nodes. Although some earlier workers suggested that such activation may be related to the presence of lymphoid cells,22 the nature of the activation process, and the specific signals which induce it were unknown. However, it has recently become apparent from studies on endothelial cultures that many of these functional and morphological effects can be induced in vitro by purified lymphokines, monokines, and by other stimuli. This process of endothelial activation represents either a marked stimulation of constitutive functions of the endothelium or the induction of new activities and molecules. In this chapter we shall briefly review the effects of well-characterized cytokines on endothelial function, morphology, and antigen expression in vitro, and examine the role of endothelial activation in several clinical settings in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aggarwal, B. B., Fessalu, T. E., and Hass, P. E., 1985, Characterization of receptors for human tumor necrosis factor and their regulation by γ-interferon, Nature 318:665

    Article  PubMed  CAS  Google Scholar 

  2. Auron, P. E., Webb, A. C., Rosenwasser, L. J., Mucci, S. F., Rich, A., Wolff, S. M., and Dinarello, C. A., 1984, Nucleotide sequence of human monocyte interleukin 1 precursor cDNA, Proc. Natl. Acad. Sci. USA 81:7907.

    Google Scholar 

  3. Banda, M. J., Knighton, D. R., Hunt, T. K., and Werb, Z., 1982, Isolation of a nonmitogenic angiogenesis factor from wound fluid, Proc. Natl. Acad. Sci. USA 79:7773.

    Google Scholar 

  4. Beck, G., Habicht, G. S., Benach, J. L., andMiller, F., 1986, Interleukin 1: A common endogenous mediator of inflammation and the local Shwartzman phenomenon, J. Immunol. 136:3025.

    PubMed  CAS  Google Scholar 

  5. Beutler, B., andCerami, A., 1987, Cachectin: More than a tumor necrosis factor, N. Engl. J. Med. 316:379.

    Article  PubMed  CAS  Google Scholar 

  6. Bevilacqua, M. P., Pober, J. S., Majeau, G. R., Cotran, R. S., andGimbrone, M. A.,Jr., 1984, Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells, J. Exp. Med. 160:618.

    Article  PubMed  CAS  Google Scholar 

  7. Bevilacqua, M. P., Pober, J. S., Wheeler, M. E., Cotran, R. S., andGimbrone, M. A., Jr., 1985, Interleukin-1 acts on cultured human vascular endothelial cells to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines, J. Clin. Invest. 76:2003.

    Article  PubMed  CAS  Google Scholar 

  8. Bevilacqua, M. P., Pober, J. S., Majeau, G. R., Fiers, W., Cotran, R. S., and Gimbrone, M. A., Jr., 1986, 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.

    Google Scholar 

  9. Bevilacqua, M. P., Schleef, R. R., Gimbrone, M. A., Jr.,andLoskutoff, D. J., 1986, Regulation of fibrinolytic system of cultured human vascular endothelium by interleukin 1,J. Clin. Invest. 78:587.

    Article  PubMed  CAS  Google Scholar 

  10. Bevilacqua, M. P., Pober, J. S., Mendrick, D. L., Cotran, R. S., and Gimbrone, M. A., Jr., 1987, Identification of an inducible endothelial-leukocyte adhesion molecule, Proc. Natl. Acad. Sci USA 84:9238.

    Google Scholar 

  11. Collins, T., Korman, A. J., Wake, C. T., Boss, J. M., Kappes, D. J., Fiers, W., Ault, K. A., Gimbrone, M. A., Jr., Strominger, J. L., and Pober, J. S., 1984, Immune interferon cultivates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts, Proc. Natl. Acad. Sci. USA 81:4917.

    Google Scholar 

  12. Collins, T., Lapierre, L. A., Fiers, W., Strominger, J. L., and Pober, J. S., 1986, Recombinant human tumor necrosis factor increases on RNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro, Proc. Natl. Acad. Sci. USA 83:446.

    Google Scholar 

  13. Cotran, R. S., Gimbrone, M. A., Jr., Bevilacqua, M. P., Mendrick, D. L.,andPober, J. S., 1986, Induction and detection of a human endothelial activation antigen in vivo, J. Exp. Med. 164:661.

    Article  PubMed  CAS  Google Scholar 

  14. Cotran, R. S., Stavrakis, G., Pober, J. S., Gimbrone, M. A., Jr., Mendrick, D. L., Mihm, M. C., Jr.,andPinkus, G. S., 1987, Endothelial activation: Identification in lesions of lymph nodes and skin, Lab. Invest. 56:16A.

    Google Scholar 

  15. Dower, S. K., Kronheim, S. R., Hopp, T. P., Cantrell, M., Deeley, M., Gillis, S., Henney, C. S., andUrdal, D. L., 1986, The cell surface receptor for interleukin-lα and interleukin-1β are identical, Nature 324:266.

    Article  PubMed  CAS  Google Scholar 

  16. Dumonde, D. C., Pulley, M. S., Paradinas, F. J., Soutcott, B. M., O’Connell, D., Robinson, M. R. G., DenHollander, F., andScuurs, A. H., 1982, Histological features of skin reactions to human lymphoid cell line lympholine in patients with advanced cancer, J. Pathol. 138:289.

    Article  PubMed  CAS  Google Scholar 

  17. Dustin, M. L., Rothlein, R., Bhan, A. K., Dinarello, C. A., andSpringer, T. A., 1986, Induction by IL-1 and interferon-γ, tissue distribution, biochemistry and function of a natural adherence molecule (ICAM-1), J. Immunol. 137:245.

    PubMed  CAS  Google Scholar 

  18. Dvorak, H. F., Galli, S. J., andDvorak, A. M., 1986, Cellular and vascular manifestations of cellmediated immunity, Hum. Pathol. 17:124.

    Article  Google Scholar 

  19. Emeis, J. J., andKooistra, T., 1986, Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells, J. Exp. Med. 163:1260. Folkman, J., and Klagsbara, M., 1987, Angiogenic factors, Science 235:442.

    Article  Google Scholar 

  20. Gamble, J. R., Harlan, J. M., Klebanoff, S. J., and Vadas, M. A., 1985, Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor, Proc. Natl. Acad. Sci. USA 82:8667.

    Google Scholar 

  21. Gell, P. G. H., 1958, Cytologic events in hypersensitivity reactions, in: Cellular and Vascular Aspects of Hypersensitivity States (H.S. Lawrence), Harper & Row, New York.

    Google Scholar 

  22. Geppert, T. D., andLipsky, P. E., 1985, Antigen presentation by interferon-γ-treated endothelial cells and fibroblasts: Differential ability to function as antigen-presenting cells despite comparable la expression, J. Immunol. 135:3750.

    PubMed  CAS  Google Scholar 

  23. Gray, P. W., Aggarwal, B. B., Benton, C. V., Bringman, T. S., Herzel, W. J., Jarrett, J. A., Leung, D. W., Moffat, B., Ng, P., Dvedersky, L. P., Palladino, M. A., andNedwin, G. E., 1984, Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumor necrosis activity, Nature 312:721.

    Article  PubMed  CAS  Google Scholar 

  24. Groenewegen, G., Buurman, W. A., andVan der Linden, C. J., 1985, Lymphokine dependence in vivo expression of MHC class II antigens by endothelium, Nature 316:361.

    Article  PubMed  CAS  Google Scholar 

  25. Kurt-Jones, E. A., Fiers, W., and Pober, J. S., 1987, Membrane interleukin 1 induction on human endothelial cells and dermal fibroblasts. J. Immunol. 139:2317.

    PubMed  CAS  Google Scholar 

  26. Leung, D. Y. M., Collins, T., Lapierre, L. A., Geha, R. S., andPober, J. S., 1986, Immunoglobulin M antibodies present in the acute phase of Kawasaki syndrome lyse cultured vascular endothelial cells stimulated by gamma interferon, J. Clin. Invest. 77:1428.

    Article  PubMed  CAS  Google Scholar 

  27. Leung, D. Y. M., Geha, R. S., Newburger, J. W., Burns, J. C., Fiers, W., Lapierre, L. A., andPober, J. S., 1986, Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome, J. Exp. Med. 164:1958.

    Article  PubMed  CAS  Google Scholar 

  28. Libby, P., Ordovas, J. M., Auger, K. R., Robbins, A. H., Birinyi, L. K., andDinarello, C. A., 1986, Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells, Am. J. Pathol. 124:179.

    PubMed  CAS  Google Scholar 

  29. March, C. J., Mosley, B., Larsen, A., Cerretti, D. P., Braedt, G., Price, V., Gillis, S., Henney, C. S., Kronheim, S. R., Grabstein, K., Conlon, P. J., Hopp,T. P., andCosman, D., 1985, Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs, Nature 315:641.

    Article  PubMed  CAS  Google Scholar 

  30. Martin, B. M., Gimbrone, M. A., Jr., Unanue, E. R., and Cotran, R. S., 1981, Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor, J. Immunol. 126:1510.

    PubMed  CAS  Google Scholar 

  31. Matsushima, K., Akahoshi, T., Yamada, M., Furutani, Y., andOppenheim, J. J., 1986, Properties of a specific interleukin 1 (IL 1) receptor on human Epstein-Barr virus transformed B lymphocytes: Identity of the receptor for IL 1-α and IL 1-β, J. Immunol. 136:4496.

    PubMed  CAS  Google Scholar 

  32. Miossec, P., Cavender, D., and Ziff, M., 1986, Production of interleukin 1 by human endothelial cells, J. Immunol. 136:2486.

    PubMed  CAS  Google Scholar 

  33. Nachman, R. L., Hajjar, K. A., Silverstein, R. L., andDinarello, C. A., 1986, Interleukin 1 induces endothelial cell synthesis of plasminogen activator inhibitor, J. Exp. Med. 163:1595.

    Article  PubMed  CAS  Google Scholar 

  34. Nawroth, P. P., andStern, D. M., 1986, Modulation of endothelial cell hemostatic properties by tumor necrosis factor, J. Exp. Med. 163:740.

    Article  PubMed  CAS  Google Scholar 

  35. Nawroth, P. P., Handley, D. A., Esmon, C. T., and Stern, D. M., 1986, Interleukin 1 induces endothelial cell-surface anticoagulant activity, Proc. Natl. Acad. Sci. USA 83:3460.

    Google Scholar 

  36. Nawroth, P. P., Bank, I., Handley, D., Cassimeris, J., Chess, L., andStern, D., 1986, Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1, J. Exp. Med. 163:1363.

    Article  PubMed  CAS  Google Scholar 

  37. Nawroth, P. P., Handley, C. T., Esmon, C., and Stern, D., 1986, Interleukin 1 induces endothelial cell procoagulant activity while suppressing cell surface anticoagulant activity, Proc. Natl. Acad. Sci. USA 83:3460.

    Google Scholar 

  38. Old, L. J., 1985, Tumor necrosis factor (TNF),Science 230:630.

    Article  PubMed  CAS  Google Scholar 

  39. Oppenheim, J. J., Kovacs, E. J., Matsushima, K., andDurum, S. K., 1986, There is more than one interleukin 1, Immunol. Today 7:45.

    Article  CAS  Google Scholar 

  40. Pennica, D., Nedwin, G. E., Hayflick, J. S., Seeburg, P. H., Derynk, R., Palladino, M. A., Kohr, W. J., Aggarwal, B. B., andGoeddel, D. V., 1984, Human tumor necrosis factor: Precursor structure, expression, and homology to lymphotoxin, Nature 312:724.

    Article  PubMed  CAS  Google Scholar 

  41. Pober, J. S., Gimbrone, M. A., Jr., Cotran, R. S., Reiss, C. S., Burakoff, S. J., Fiers, W., and Ault, K. A., 1983, la expression by vascular endothelium is inducible by activated T cells and by human γ interferon, J. Exp. Med. 157:1339.

    Article  PubMed  CAS  Google Scholar 

  42. Pober, J. S., Collins, T., Gimbrone, M. A., Jr., Cotran, R. S., Gitlin, J. D., Fiers, W., Clayberger, C., Krensky, A. M., Burakoff, S. J., and Reiss, C. S., 1983, Lymphocytes recognize human vascular endothelial and dermal fibroblast la antigens induced by recombinant immune interferon, Nature 305:726.

    Article  PubMed  CAS  Google Scholar 

  43. . Pober, J. S., Collins, T., Gimbrone, M. A., Jr., Libby, P., and Reiss, C. S., 1986, Overview: Inducible expression of class II major histocompatibility complex antigens and the immunogenicity of vascular endothelium, Transplantation 41:141.

    Article  PubMed  CAS  Google Scholar 

  44. Pober, J. S., Gimbrone, M. A., Jr., Lapierre, L. A., Mendrick, D. L., Fiers, W., Rothlein, R., and Springer, T. A., 1986, Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor and immune interferon, J. Immunol. 137:1893.

    PubMed  CAS  Google Scholar 

  45. Pober, J. S., Bevilacqua, M. P., Mendrick, D. L., Lapierre, L. A., Fiers, W., and Gimbrone, M. A., Jr., 1986, 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.

    PubMed  CAS  Google Scholar 

  46. Pober, J. S., Lapierre, L. A., Stolpen, A. H., Brock, T. A., Springer, T. A., Fiers, W., Bevilacqua, M. P., Mendrick, D. S., and Gimbrone, M. A., Jr., 1987, Activation of cultured human endothelial cells by recombinant lymphotoxin: Comparison with tumor necrosis factor and interleukin 1 species, J. Immunol. 138:3319.

    PubMed  CAS  Google Scholar 

  47. Polverini, P. J., Cotran, R. S., and Sholley, M. M., 1977, Endothelial proliferation in the delayed hypersensitivity reaction: An autoradiographic study, J. Immunol. 118:529.

    PubMed  CAS  Google Scholar 

  48. Polverini, P. J., Cotran, R. S., Gimbrone, M. A., Jr., and Unanue, E. R., 1977, Activated macrophages induce vascular proliferation, Nature 269:804.

    Article  PubMed  CAS  Google Scholar 

  49. Ruddle, N., 1985, Lymphotoxin redux, Immunol. Today 6:156.

    Article  CAS  Google Scholar 

  50. . Sobel, R. A., Blanchette, B. W., Bhan, A. K., and Colvin, R. B., 1984, The immunopathology of experimental allergic encephalomyelitis. II. Endothelial cell la increases prior to inflammatory cell infiltration, J. Immunol. 132:2402.

    PubMed  CAS  Google Scholar 

  51. Stern, D. M., Bank, I., Nawroth, P. P., Cassimeris, J., Kisiel, W., Fenton, J. W., Dinarello, C. A., Chess, L., and Jaffe, E. A., 1985, Self regulation of procoagulant events on the endothelial cell surface, J. Exp. Med. 162:1223.

    Article  PubMed  CAS  Google Scholar 

  52. Stolpen, A. H., Guinan, E. C., Fiers, W., and Pober, J. S., 1986, Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human endothelial cell monolayers, Am. J. Pathol. 123:16.

    PubMed  CAS  Google Scholar 

  53. Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., III, Zentella, A., Albert, J. D., Shires, G. T., and Cerami, A., 1986, Shock and tissue injury induced by recombinant cachectin, Science 234:470.

    Article  PubMed  CAS  Google Scholar 

  54. Trinchieri, G., and Perussia, B., 1985, Immune interferon: A pleiotropic lymphokine with multiple effects, Immunol. Today 6:131.

    Article  CAS  Google Scholar 

  55. Wagner, C. R., Vetto, R. M., and Burger, D. R., 1985, Expression of I-region associated antigen (la) and interleukin 1 by subcultural human endothelial cells, Cell. Immunol. 93:91.

    Article  PubMed  CAS  Google Scholar 

  56. Watt, S. L., and Auerbach, R., 1986, A mitogenic factor for endothelial cells obtained from mouse secondary mixed leukocyte cultures, J. Immunol. 136:197.

    PubMed  CAS  Google Scholar 

  57. Wiener, J., Lattes, R. G., and Spiro, D., 1967, An electron microscopic study of leukocyte emigration and vascular permeability in tubercalia sensitivity, Am. J. Pathol. 50:485.

    PubMed  CAS  Google Scholar 

  58. Willms-Kretschmer, K., Flax, M. H., and Cotran, R. S., 1967, The fine structure of the vascular response in hapten-specific delayed hypersensitivity and contact dermatitis, Lab. Invest. 17:334.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA

    Ramzi S. Cotran & Jordan S. Pober

Authors
  1. Ramzi S. Cotran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jordan S. Pober
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Cellular Biology and Pathology, Bucharest, Romania

    Nicolae Simionescu  & Maya Simionescu  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Plenum Press, New York

About this chapter

Cite this chapter

Cotran, R.S., Pober, J.S. (1988). Endothelial Activation. In: Simionescu, N., Simionescu, M. (eds) Endothelial Cell Biology in Health and Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0937-6_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0937-6_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8254-9

  • Online ISBN: 978-1-4613-0937-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation