Skip to main content
Immunology logoLink to Immunology
. 1992 Dec;77(4):543–549.

E-selectin and intercellular adhesion molecule-1 are released by activated human endothelial cells in vitro.

J F Leeuwenberg 1, E F Smeets 1, J J Neefjes 1, M A Shaffer 1, T Cinek 1, T M Jeunhomme 1, T J Ahern 1, W A Buurman 1
PMCID: PMC1421640  PMID: 1283598

Abstract

Endothelial cells respond to several cytokines by a rapid increase in expression of the adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1), followed by a gradual decline. The fate of these molecules, which was so far unknown, was studied. Specific sandwich ELISA for the detection of soluble (s)E-selectin and sICAM-1 were developed. In supernatant, centrifuged 3 hr at 100,000 g to remove microparticles, from human umbilical vein endothelial cells (HUVEC) activated with tumour necrosis factor (TNF), interleukin-1 (IL-1) or lipopolysaccharide (LPS), E-selectin and ICAM-1 molecules could be detected. Biochemical analysis revealed that sE-selectin migrated as a band of approximately 94,000 MW. The amount of soluble adhesion molecules released was directly correlated with cell surface expression. Maximal release of E-selectin was observed 6-12 hr after activation of HUVEC and decreased to below detection limit 24 hr after activation. After activation, release of ICAM-1 gradually increased with ICAM-1 cell surface expression, and reached a plateau after 24 hr, which was constant for 3 days. Since E-selectin and ICAM-1 are highly expressed at inflammatory sites, the resulting high concentrations of released E-selectin and ICAM-1 may affect interactions of leucocytes with endothelial cells. The physiological role, however, of the release of E-selectin and ICAM-1 remains to be elucidated.

Full text

PDF
543

Images in this article

Selected References

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

  1. Adams D. H., Hubscher S. G., Shaw J., Rothlein R., Neuberger J. M. Intercellular adhesion molecule 1 on liver allografts during rejection. Lancet. 1989 Nov 11;2(8672):1122–1125. doi: 10.1016/s0140-6736(89)91489-x. [DOI] [PubMed] [Google Scholar]
  2. Becker J. C., Dummer R., Hartmann A. A., Burg G., Schmidt R. E. Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha. Functional consequences on cell-mediated cytotoxicity. J Immunol. 1991 Dec 15;147(12):4398–4401. [PubMed] [Google Scholar]
  3. Berg M., James S. P. Human neutrophils release the Leu-8 lymph node homing receptor during cell activation. Blood. 1990 Dec 1;76(11):2381–2388. [PubMed] [Google Scholar]
  4. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  6. Carlos T., Kovach N., Schwartz B., Rosa M., Newman B., Wayner E., Benjamin C., Osborn L., Lobb R., Harlan J. Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1. Blood. 1991 May 15;77(10):2266–2271. [PubMed] [Google Scholar]
  7. Cotran R. S., Gimbrone M. A., Jr, Bevilacqua M. P., Mendrick D. L., Pober J. S. Induction and detection of a human endothelial activation antigen in vivo. J Exp Med. 1986 Aug 1;164(2):661–666. doi: 10.1084/jem.164.2.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dobberstein B., Garoff H., Warren G., Robinson P. J. Cell-free synthesis and membrane insertion of mouse H-2Dd histocompatibility antigen and beta 2-microglobulin. Cell. 1979 Aug;17(4):759–769. doi: 10.1016/0092-8674(79)90316-7. [DOI] [PubMed] [Google Scholar]
  9. Dunlop L. C., Skinner M. P., Bendall L. J., Favaloro E. J., Castaldi P. A., Gorman J. J., Gamble J. R., Vadas M. A., Berndt M. C. Characterization of GMP-140 (P-selectin) as a circulating plasma protein. J Exp Med. 1992 Apr 1;175(4):1147–1150. doi: 10.1084/jem.175.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dustin M. L., Springer T. A. Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol. 1988 Jul;107(1):321–331. doi: 10.1083/jcb.107.1.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Engelberts I., Samyo S. K., Leeuwenberg J. F., van der Linden C. J., Buurman W. A. A role for ELAM-1 in the pathogenesis of MOF during septic shock. J Surg Res. 1992 Aug;53(2):136–144. doi: 10.1016/0022-4804(92)90025-u. [DOI] [PubMed] [Google Scholar]
  12. Groves R. W., Allen M. H., Barker J. N., Haskard D. O., MacDonald D. M. Endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in cutaneous inflammation. Br J Dermatol. 1991 Feb;124(2):117–123. doi: 10.1111/j.1365-2133.1991.tb00419.x. [DOI] [PubMed] [Google Scholar]
  13. Harning R., Mainolfi E., Bystryn J. C., Henn M., Merluzzi V. J., Rothlein R. Serum levels of circulating intercellular adhesion molecule 1 in human malignant melanoma. Cancer Res. 1991 Sep 15;51(18):5003–5005. [PubMed] [Google Scholar]
  14. Johnson J. P., Stade B. G., Holzmann B., Schwäble W., Riethmüller G. De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci U S A. 1989 Jan;86(2):641–644. doi: 10.1073/pnas.86.2.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jutila M. A., Rott L., Berg E. L., Butcher E. C. Function and regulation of the neutrophil MEL-14 antigen in vivo: comparison with LFA-1 and MAC-1. J Immunol. 1989 Nov 15;143(10):3318–3324. [PubMed] [Google Scholar]
  16. Kuijpers T. W., Hakkert B. C., Hoogerwerf M., Leeuwenberg J. F., Roos D. Role of endothelial leukocyte adhesion molecule-1 and platelet-activating factor in neutrophil adherence to IL-1-prestimulated endothelial cells. Endothelial leukocyte adhesion molecule-1-mediated CD18 activation. J Immunol. 1991 Aug 15;147(4):1369–1376. [PubMed] [Google Scholar]
  17. Leeuwenberg J. F., Jeunhomme G. M., Buurman W. A. Adhesion of polymorphonuclear cells to human endothelial cells. Adhesion-molecule-dependent, and Fc receptor-mediated adhesion-molecule-independent mechanisms. Clin Exp Immunol. 1990 Sep;81(3):496–500. doi: 10.1111/j.1365-2249.1990.tb05362.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leeuwenberg J. F., Jeunhomme G. M., Buurman W. A. Characterization of two monoclonal antibodies directed against an adhesion molecule on human endothelial cells. Transplant Proc. 1990 Aug;22(4):1991–1993. [PubMed] [Google Scholar]
  19. Leeuwenberg J. F., Jeunhomme T. M., Buurman W. A. Induction of an activation antigen on human endothelial cells in vitro. Eur J Immunol. 1989 Apr;19(4):715–720. doi: 10.1002/eji.1830190422. [DOI] [PubMed] [Google Scholar]
  20. Leeuwenberg J. F., Jeunhomme T. M., Buurman W. A. Role of ELAM-1 in adhesion of monocytes to activated human endothelial cells. Scand J Immunol. 1992 Mar;35(3):335–341. doi: 10.1111/j.1365-3083.1992.tb02866.x. [DOI] [PubMed] [Google Scholar]
  21. Leeuwenberg J. F., Van Damme J., Meager T., Jeunhomme T. M., Buurman W. A. Effects of tumor necrosis factor on the interferon-gamma-induced major histocompatibility complex class II antigen expression by human endothelial cells. Eur J Immunol. 1988 Sep;18(9):1469–1472. doi: 10.1002/eji.1830180925. [DOI] [PubMed] [Google Scholar]
  22. Lo S. K., Lee S., Ramos R. A., Lobb R., Rosa M., Chi-Rosso G., Wright S. D. Endothelial-leukocyte adhesion molecule 1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, alpha m beta 2) on human neutrophils. J Exp Med. 1991 Jun 1;173(6):1493–1500. doi: 10.1084/jem.173.6.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lobb R. R., Chi-Rosso G., Leone D. R., Rosa M. D., Bixler S., Newman B. M., Luhowskyj S., Benjamin C. D., Dougas I. G., Goelz S. E. Expression and functional characterization of a soluble form of endothelial-leukocyte adhesion molecule 1. J Immunol. 1991 Jul 1;147(1):124–129. [PubMed] [Google Scholar]
  24. Munro J. M., Pober J. S., Cotran R. S. Tumor necrosis factor and interferon-gamma induce distinct patterns of endothelial activation and associated leukocyte accumulation in skin of Papio anubis. Am J Pathol. 1989 Jul;135(1):121–133. [PMC free article] [PubMed] [Google Scholar]
  25. Neefjes J. J., Ploegh H. L. Allele and locus-specific differences in cell surface expression and the association of HLA class I heavy chain with beta 2-microglobulin: differential effects of inhibition of glycosylation on class I subunit association. Eur J Immunol. 1988 May;18(5):801–810. doi: 10.1002/eji.1830180522. [DOI] [PubMed] [Google Scholar]
  26. Picker L. J., Kishimoto T. K., Smith C. W., Warnock R. A., Butcher E. C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991 Feb 28;349(6312):796–799. doi: 10.1038/349796a0. [DOI] [PubMed] [Google Scholar]
  27. Redl H., Dinges H. P., Buurman W. A., van der Linden C. J., Pober J. S., Cotran R. S., Schlag G. Expression of endothelial leukocyte adhesion molecule-1 in septic but not traumatic/hypovolemic shock in the baboon. Am J Pathol. 1991 Aug;139(2):461–466. [PMC free article] [PubMed] [Google Scholar]
  28. Rothlein R., Czajkowski M., O'Neill M. M., Marlin S. D., Mainolfi E., Merluzzi V. J. Induction of intercellular adhesion molecule 1 on primary and continuous cell lines by pro-inflammatory cytokines. Regulation by pharmacologic agents and neutralizing antibodies. J Immunol. 1988 Sep 1;141(5):1665–1669. [PubMed] [Google Scholar]
  29. Rothlein R., Dustin M. L., Marlin S. D., Springer T. A. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986 Aug 15;137(4):1270–1274. [PubMed] [Google Scholar]
  30. Rothlein R., Mainolfi E. A., Czajkowski M., Marlin S. D. A form of circulating ICAM-1 in human serum. J Immunol. 1991 Dec 1;147(11):3788–3793. [PubMed] [Google Scholar]
  31. Seth R., Raymond F. D., Makgoba M. W. Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders. Lancet. 1991 Jul 13;338(8759):83–84. doi: 10.1016/0140-6736(91)90077-3. [DOI] [PubMed] [Google Scholar]
  32. Shimizu Y., Shaw S., Graber N., Gopal T. V., Horgan K. J., Van Seventer G. A., Newman W. Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature. 1991 Feb 28;349(6312):799–802. doi: 10.1038/349799a0. [DOI] [PubMed] [Google Scholar]
  33. Smith W. B., Gamble J. R., Clark-Lewis I., Vadas M. A. Interleukin-8 induces neutrophil transendothelial migration. Immunology. 1991 Jan;72(1):65–72. [PMC free article] [PubMed] [Google Scholar]
  34. Vejlsgaard G. L., Ralfkiaer E., Avnstorp C., Czajkowski M., Marlin S. D., Rothlein R. Kinetics and characterization of intercellular adhesion molecule-1 (ICAM-1) expression on keratinocytes in various inflammatory skin lesions and malignant cutaneous lymphomas. J Am Acad Dermatol. 1989 May;20(5 Pt 1):782–790. doi: 10.1016/s0190-9622(89)70090-6. [DOI] [PubMed] [Google Scholar]
  35. Wheeler M. E., Luscinskas F. W., Bevilacqua M. P., Gimbrone M. A., Jr Cultured human endothelial cells stimulated with cytokines or endotoxin produce an inhibitor of leukocyte adhesion. J Clin Invest. 1988 Oct;82(4):1211–1218. doi: 10.1172/JCI113718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. van de Rijn M., Geurts van Kessel A. H., Kroezen V., van Agthoven A. J., Verstijnen K., Terhorst C., Hilgers J. Localization of a gene controlling the expression of the human transferrin receptor to the region q12 leads to qter of chromosome 3. Cytogenet Cell Genet. 1983;36(3):525–531. doi: 10.1159/000131967. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES