Leukocyte integrin activation

The term ‚integrin’ was proposed by Richard Hynes to describe a family of integral membrane receptors thought to link or “integrate” the cytoskeleton of one cell with that of another cell or with the extracellular matrix [1]. Much has yet to be learned about their intracellular connections, but the participation of these receptors in cell-matrix and cell-cell interactions has been well documented in many recent reviews [2–9]. The integrins comprise a superfamily of heterodimers composed of noncovalently-associated α and β subunits, both of which are transmembrane proteins (Fig. 1). Initially these receptors were divided into three groups based on the sharing of a common β subunit (β1, β2 or β3) by various α subunits. These groups were named the VLA proteins (β1 type), leukocyte integrins (CD11/CD 18 family; β2 type) and thirdly, the cytoadhesins (β3 type) consisting of platelet GPIIbIIIa and the vitronectin receptor. Now seven β subunits have been clearly defined, and genomic analysis suggests that there may be at least 15 of these subunits. In addition, new a subunits are in the process of being characterized. A further complexity arises from variable splicing, which so far has been localized to the cytoplasmic sequences of β subunits. It was originally thought that the α subunits within each group bonded faithfully to an individual β subunit, but it is now apparent that alternative pairings are possible. Although specificity for ligand is chiefly dictated by the α subunit, association with different β subunits would appear to provide a further level of specificity. For example, αv of the vitronectin receptor (VNR) can combine with β3 to recognize the matrix proteins fibronectin, fibrinogen and vitronectin, with β5 to recognize fibronectin and vitronectin and in a kidney cell line, with β1 to recognise vitronectin only [10]