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)

Abstract

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.

Keywords

Integrin Thrombocytopenia Leucine Fibrinogen Laminin 

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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

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