Are Free Radicals Involved in the Expression of Adhesion Molecules?

  • W. Sluiter
  • A. Pietersma
  • J. F. Koster
Part of the NATO ASI Series book series (NSSA, volume 296)


It is beyond doubt that the adhesion of leukocytes to the endothelial lining of the vascular wall plays a key role in various biological processes, including inflammation and thrombosis. This phenomenon is the result of a complex interplay among blood flow, cell adhesion and molecular vascular biology factors. Normally, the circulating granulocytes and monocytes in peripheral blood are distributed over a circulating pool and a marginating pool. The marginating pool comprises about 60% of the total number of cells (Athens, Raab, Haab, Aschenbrucker, and Cartwright, 1961; Van Furth and Sluiter, 1986). The leukocytes of the marginating pool roll along the endothelial line of the vessel. This rolling is governed by the shear force of the flowing blood and the strength of the ionic bonds with the vascular endothelium (Tangelden and Afors, 1991). Under inflammatory conditions the number of rolling leukocytes in the postcapillary vesicles increases drastically. Those leukocytes adhere selectively to the endothelium. Next, these cells traverse the vessel wall between adjacent endothelial cells keeping the monolayer intact, pass the subendothelial layer and accumulate at the site of the inflammation. Strinkingly, granulocytes are commonly the first cells here, followed by the monocytes. It is obvious that knowledge of the mechanism(s) by which granulocytes and monocytes adhere to the vessel wall will enlarge therapeutic modalities (Sluiter, Pietersma, Lamers, and Koster, 1993).


Leukocyte Adhesion Vascular Cell Adhesion Molecule Nuclear Factor kappaB Cytochrome P450 Monooxygenase Leukocyte Adhesion Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Athens, J.W., Raab, S.O., Haab, O.P., Mauer, A.M., Aschenbrucker, and Cartwright, G.E., 1961, Leukokinetic studies III. The distribution of granulocytes in the blood of normal subjects, J. Clin. Invest. 40: 159–168.Google Scholar
  2. Carlos, T.M., and Harlan, J.M., 1994, Leukocyte-endothelial adhesion molecules. Blood 84: 2068–2101.Google Scholar
  3. Collins, T., Read, M.A., Neish, A.S., Whitley, M.Z., Thonos, D., and Maniates, T., 1995, Transcriptional regulation of endothelial cell adhesion molecules:NF kappaB cytokine-induced enhancers, FASEB J. 9: 899–909.Google Scholar
  4. Cybulsky, M.I., and Gimbrone, M.A., 1991, Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis, Science 251: 788–791.CrossRefGoogle Scholar
  5. De Fougerolles, A.R., Stacker, S.A., Schawarting, R., and Springer, T.A., 1991, Characterization of ICAM-2 and evidence for a third counter receptor for LFA-I, J. Exp. Med. 174: 253–267.CrossRefGoogle Scholar
  6. Dustin, M.L., Staunton, D.E., and Springer, T.A., 1988, Supergene families meet in the immune system, Immunol. Today 9: 213–215.CrossRefGoogle Scholar
  7. Irani, K., Xia, Y., Zweier, J.L., Sollalt, S.J., Der, C.J., Fearon, E.R., Sunderesan, M., Finkel, T., and GoldschmidtClermont, P.J., 1997, Mitogenic signaling mediated by oxidants in Res transformed fibroblasts. Science 275: 1649–1652.Google Scholar
  8. Khan, B.V., Harrison, D.G., Oblrych, M.T., Alexander, R.W., and Medford, R.M., 1996, Nitric oxide regulates vascular cell adhesion molecule-1 gene expression and redox sensitive transcriptional events in human vesicles endothelial cells, Proc. Natl. Acad. Sci. USA 93: 9114–9119.CrossRefGoogle Scholar
  9. Liu, Z-G., Hsu, H., Goedelel, D.V., and Karim, A., 1996, Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappa-B activation prevents cell death, Cell 87: 565–576.CrossRefGoogle Scholar
  10. Matsubara, T., and Ziff, M., 1986, Increased superoxide anion release from human endothelial cells in response to cytokines, J. Immunol. 137: 3296–3298.Google Scholar
  11. Neish, A.S., Williams, A.J., Palmer, H.J., Whitley, M.J., and Collins, T., 1992, Functional analysis of the humen vascular cell adhesion molecule-la promotor. J. Exp. Med. 176: 1583–1593.CrossRefGoogle Scholar
  12. Osborn, L., Hession, C., Tizard, R., Vasselo, C., Bubewsky, S., Chi-Rosso, G., and Lobb, R., 1989, Direct expression cloning of vascular cell adhesion molecule-1, a cytokine-induced endothelial protein that binds lymphocytes, Cell 59: 1203–1211.CrossRefGoogle Scholar
  13. Picker, L.J., Warnssoek, R.A., Burns, A.R., Doerschaak, C.M., Berg, E.L., Butcher, E.C., 1991, The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140, Cell 66: 921–933.CrossRefGoogle Scholar
  14. Pietersma, A., Tilly, B.C., Gaestel, M., De Jong, N., Lee, J.C., Koster, J.F., and Sluiter, W., 1997, P38 mitogen activated protein kinase regulated endothelial VCAM-I expression at the posttranscriptional level, Biochem. Biophys. Res. Commun. 230: 44–48.CrossRefGoogle Scholar
  15. Rice, C.E., Munro, J.M., Carlos, C., Bevilacqa, M., 1991, Vascular and non-vascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissues. Am. J. Pathol. 138: 385–393.Google Scholar
  16. Royall, J.A., Gwin, P.D., Packs, D.A., Freeman, B.A., 1992, Responses of vascular endothelial metabolism to lipopolysaccharide and tumor necrosis factor alpha, Arch. Biochem. Biophys. 294: 686–699.CrossRefGoogle Scholar
  17. Schreck, R., Albermann, K., and Baeuerle, P.A., 1992, Nuclear factor kappa-B: an oxidative stress responsive transcription factor of eukaryotic cells (a review), Free Rad Res. Commun. 4: 221–237.CrossRefGoogle Scholar
  18. Sluiter, W., Pietersma, A.,Lamers, J.M.J., and Koster, J.F., 1993, Leukocyte adhesion molecules on the vascular endothelium. Their role in the pathogenesis of cardiovascular disease and the mechanism underlying their expression, J. Cardiol. Pharmacol. 22: S37 - S44.Google Scholar
  19. Springer, T.A., 1990, Adhesion receptors of the immune systems, Nature 346: 425–434.CrossRefGoogle Scholar
  20. Springer, T.A., 1994, Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm, Cell 76: 301–314.CrossRefGoogle Scholar
  21. Tedder, T.F.,and Penta, A.C., Levine, H.B., and Freedman, AS., 1990, Expression of the human leukocyte adhesion molecule, LAM-1. Identity with TQ1 and Leu-8 differentiation antigen. J. Immunol. 144: 532–540.Google Scholar
  22. Tengelder, G.J. Arfors, K.E., 1991, Inhibition of leukocyte rolling in venules by protamine and sulphonated polysaccharides, Blood 77: 1565–1571.Google Scholar
  23. Van Furth, R., and Sluiter, W., 1986, Distribution of blood monocytes between a marginating and a circulating pool, J. Exp. Med. 163: 474–479.CrossRefGoogle Scholar
  24. Voraberger, G., Schafer, R., and Stratowa, C., 1991, Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5’ regulatory region. Induction by cytokines and phorbol ester, J. Immunol. 147: 2777–2786.Google Scholar
  25. Weber, C., Erl, W., Pietsch, A., Ströbel, M., Ziegler-Heitbroek, H.W., and Webe, P.C., 1994, Antioxidants inhibit monocyte adhesion by suppressing nuclear factor kappaB mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals, Artheriolscler. Thromb. 14: 1665–1673.CrossRefGoogle Scholar
  26. Williams, A.F., and Barclay, A.N., 1988, The immunoglobulin superfamily-domains for cell surface recognition, Annu. Rev. Immunol. 6: 381–405.CrossRefGoogle Scholar
  27. Whelan, J. Gharsa, P., Hoeft and Huijsdwijner, R.H., Gray, J., Chandra, G., Talalat, F., and Delamarter, J.F., 1991, An NF kappaB-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription, Nucleic Acids Res. 19: 2645–2653.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • W. Sluiter
    • 1
  • A. Pietersma
    • 1
  • J. F. Koster
    • 1
  1. 1.Department of Biochemistry Cardiovascular Research Institute COEUR School of Medicine and Health SciencesErasmus University RotterdamRotterdamThe Netherlands

Personalised recommendations