Pathophysiological Significance of Endothelial Cell Integrins

  • Jan A. van Mourik
  • Jacques G. Giltay
  • Albert E. G. Kr. von dem Borne
Part of the NATO ASI Series book series (NSSA, volume 208)


At the outer surface of the endothelial cell plasma membrane a number of structurally closely related glycoprotein complexes (“integrins”) are exposed that serve an important role in mediating the anchorage of the endothelium to extracellular matrix proteins. These surface receptors have also in common that they serve as recognition sites for multivalent matrix proteins such as fibronectin, vitronectin, collagens or laminin. (Ruoslahti and Pierschbacher, 1987; Ruoshlati, 1988). Defective functioning of these surface receptors, e.g. due to structural defects or to antibody-mediated dysfunction, may, therefore, affect the integrity of the vessel wall. Although the structure and function of integrins produced by endothelial cells and a variety of other cell types have now been described in detail and their similarities in terms of structure and mode of action have been appreciated (Buck and Horwitz, 1987; Ruoshlati, 1988), insight into the pathophysiology of disorders associated with molecular defects or dysfunction of integrins is limited. Because of the wide cellular distribution and similarities in both structure and function, one would expect that a genetically determined defect of those integrins that are under the same genetic control affects the integrity of a variety of cell types. So far this has not been found. Only when the expression of certain integrins is cell-specific, as is the case with the platelet integrin glycoprotein (GP) IIb/IIIa, or the surface receptors LFA-1, Mac-1, and p150/95, (members of the integrin family which are expressed by leukocytes only), isolated, cell-specific disorders associated with a defective integrin function might be expected. Indeed, many cases of isolated platelet- and leukocyte disorders due to integrin deficiency have been identified. (Anderson and Springer, 1987, Clemetson and Luscher, 1988). Acquired integrin dysfunction, for instance, due to the formation of integrin- specific antibodies could be of broader clinical significance. For instance, several members of the integrin family show marked antigenic polymorphism, and one might expect that an immunogenic response elicited by these polymorphic determinants will lead to systemic integrin dysfunction. However, similar to the genetically determined integrin defects, such immune-mediated disorders seem in general restricted to a single cell-type (e.g. platelets; von dem Borne and Ouwehand, 1989, or leukocytes; Pischel et al., 1987). Here we wish to provide a picture of our current knowledge of genetically determined and acquired functional abnormalities of integrins expressed by vascular endothelial cells.


Beta Subunit Integrin Family Amino Acid Polymorphism Leukocyte Adhesion Deficiency Vitronectin Receptor 
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. Anderson, D.C. and Springer, T.A. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Ann. Rev. Med. 38:175, 1987.PubMedCrossRefGoogle Scholar
  2. Bray, P.F., Barsh, G., Rosa, J.-P, Luo, X.Y., Magaenis, E. and Shuman, M.A. Physical linkage of the genes for platelet membrane glycoproteins IIb and IIIa. Proc. Natl. Acad. Sci. U.S.A. 85:8683, 1988.PubMedCrossRefGoogle Scholar
  3. Bray, P.F. and Shuman, M.A. Identification of an abnormal gene for the GPIIIa subunit of the platelet fibrinogen receptor resulting in Glanzmann’s thrombasthenia. Blood 75:881, 1990.PubMedGoogle Scholar
  4. Buck, C.A. and Horwitz, A.F. Cell surface receptors for extracellular matrix molecules. Annu. Rev. Cell Biol. 3:179, 1987.PubMedCrossRefGoogle Scholar
  5. Cheresh, D.A. and Spiro, R.C. Biosynthetic and functional properties of an Arg-Gly-Aspdirected receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J. Biol. Chem. 262:17703, 1987.PubMedGoogle Scholar
  6. Clemetson, K.J. and Luscher, E.F. Membrane glycoprotein abnormalities in pathological platelets. Biochim. Biophys. Acta. 947:53, 1988.PubMedCrossRefGoogle Scholar
  7. Flug, F., Espinola, R., Liu, L.-X. and Karpatkin, S. A 33-mer peptide spanning the 33rd amino acid polymorphism leucine/proline of platelet GP IIIa is not the PLA1/A2 epitope. Clin. Res. 38:425A, 1990 (Abstract).Google Scholar
  8. Giltay, J.C, Leeksma, O.C., Breederveld, C. and van Mourik, J.A. Normal synthesis and expression of endothelial IIb/IIIa in Glanzmann’s thrombasthenia. Blood 69:809, 1987.PubMedGoogle Scholar
  9. Giltay, J.C., Leeksma, O.C., von dem Borne, A.E.G.Kr. and van Mourik, J.A. Alloantigenic composition of the endothelial vitronectin receptor. Blood 72:230, 1988.PubMedGoogle Scholar
  10. Giltay, J.C., Brinkman, H.J.M., von dem Borne, A.E.G.Kr. and van Mourik, J.A. Expression of the alloantigen Zwa on human vascular smooth muscle cells and foreskin fibroblasts. A study on normal individuals and a patient with Glanzmann’s thrombasthenia. Blood 74:965, 1989.PubMedGoogle Scholar
  11. Giltay, J.C., Brinkman, H.J.M., Vlekke, A., Kiefel, V., van Mourik, J.A. and von dem Borne, A.E.G.Kr. The platelet glycoprotein Ia-IIa-associated Br-alloantigen system is expressed by cultured endothelial cells. Br. J. Haematol. 75:557, 1990.PubMedCrossRefGoogle Scholar
  12. Ginsberg, M.H., Loftus, J.C. and Plow, E.F. Cytoadhesins, integrins and platelets. Thrombos. Haemostas. 59:1, 1988.Google Scholar
  13. Hemler, M.E., Huang, C. and Schwarz, L. The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. J. Biol. Chem. 262:3300, 1987.PubMedGoogle Scholar
  14. Hynes, R.O. Integrins: a family of cell surface receptors. Cell 48:549, 1987.PubMedCrossRefGoogle Scholar
  15. Kishimoto, T.K., Hollander, N., Roberts, T.M., Anderson, D.C. and Springer, T.A. Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency. Cell 50:193, 1987.PubMedCrossRefGoogle Scholar
  16. Kolodziej, M., Goldberger, A., Poncz, M., Newman, P.J. and Bennett, J.S. Evidence that a GP IIIa polymorphism is responsible for the PlA1 and PlA2 alloantigens by heterologous expression of the platelet GP IIIa. Clin. Res. 38:425A, 1990 (Abstract).Google Scholar
  17. Leeksma, O.C., Giltay, J.C., Zandbergen-Spaargaren, J., Modderman, P.W., van Mourik, J.A. and von dem Borne, A.E.G.Kr. The platelet alloantigen Zwa or PlA1 is expressed by cultured endothelial cells. Br. J. Haematol. 66:369, 1987.PubMedCrossRefGoogle Scholar
  18. Lyman, S., Aster, R.H. and Newman, P.J. Polymorphism of human platelet membrane glycoprotein IIb associated with the Bak a/Bak b alloantigen system. Blood 58a, 1989 (Abstract).Google Scholar
  19. Newman, P.J., Derbes, R.S. and Aster, R.H. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine 33/proline 33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J. Clin. Invest. 83:1778, 1989.PubMedCrossRefGoogle Scholar
  20. O’Toole, T.E., Loftus, J.C., Plow, E.F., Glass, A.A., Harper, J.R. and Ginsberg, M.H. Efficient surface expression of platelet GPIIb-IIIa requires both subunits. Blood 74:14, 1989.PubMedGoogle Scholar
  21. Pischel, K.D., Marlin, S.D., Springer, T.A., Woods, Jr., V.L. and Bluestein, H.G. Polymorphism of lymphocyte function-associated antigen-1 demonstrated by a lupus patient’s alloantiserum. J. Clin. Invest. 79:1607, 1987.PubMedCrossRefGoogle Scholar
  22. Rosa, J.-P., Bray, P.F., Gayet, O., Johnston, G.I., Cook, R.G., Jackson, K.W., Shuman, M.A. and McEver, R.P. Cloning of glycoprotein IIIa cDNA from human erythroleukemia cells and localization of the gene to chromosome 17. Blood 72:593, 1988.PubMedGoogle Scholar
  23. Ruoslahti, E. and Pierschbacher, M.D. New perspectives in cell adhesion: RGD and integrins. Science 238:491, 1987.PubMedCrossRefGoogle Scholar
  24. Ruoslahti, E. Fibronectin and its receptors. Annu. Rev. Biochem. 57:375, 1988.PubMedCrossRefGoogle Scholar
  25. Ruoslahti, E. and Giancotti, F.G. Integrins and tumor cell dissemination. Cancer Cells 1:119, 1989.PubMedGoogle Scholar
  26. Shulman, N.R. and Jordan Jr., J.V. Platelet immunology. In: Hemostasis and Thrombosis, Basic Principles and Clinical Practice. Ed by J. Hirsh, V.J. Marder and E.W. Salzman. Lippincott Company, Philadelphia, pp. 452–529, 1987.Google Scholar
  27. Springer, T.A., Dustin, M.L., Kishimoto, T.K. and Martin, S.D. The lymphocyte function associated LFA-1, CD2 and LFA-3 molecules; cell adhesion receptors of the immune system. Annu. Rev. Immunol. 5:223, 1987.PubMedCrossRefGoogle Scholar
  28. Staunton, D.E., Dustin, M.L. and Springer, T.A. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature 339:61, 1989.PubMedCrossRefGoogle Scholar
  29. von dem Borne, A.E.G.Kr. and Ouwehand, W.H. Immunology of platelet disorders. In: Bailliere’s Clinical Haematology, (Ed. Caen, J.P.), Tindall, London, pp 749–781, 1989.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Jan A. van Mourik
    • 1
  • Jacques G. Giltay
    • 1
  • Albert E. G. Kr. von dem Borne
    • 1
  1. 1.Blood Transfusion ServiceCentral Laboratory of the Netherlands Red CrossAmsterdamThe Netherlands

Personalised recommendations