Functional role of α2/β1 and α4/β1 integrins in leukocyte intercellular adhesion induced through the common β1 subunit

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Abstract
Whereas all of the integrins in the VLA protein subfamily are involved in cell-extracellular matrix interactions, only VLA-4 (through the α4 subunit) has been implicated in the triggering of intercellular adhesion. Here we describe that the VLA protein β1 subunit (CD29) is also involved in the induction of homotypic cell aggregation. We have obtained three novel anti-β1 monoclonal antibodies (mAb) with the ability to induce cell aggregation on different leukocyte cell types. These mAb recognize an antigenic site on the common β1 chain of VLA proteins which is topographically and/or functionally distinct from other epitopes previously defined by several prototype anti-β1 mAb. Induction of cell aggregation by anti-β1 mAb is epitope specific, isotype and Fc independent, and displays kinetics similar to α4-mediated aggregation. This cell aggregation requires an intact cellular metabolism, the presence of divalent cations in the extracellular medium, and the integrity of the cytoskeleton. We also have found that the Na+/H+ antiporter may be essential for this process. For Ramos cells, which bear only the VLA α4/β1 heterodimer, intercellular adhesion induced through the VLA-β1 chain could be selectively inhibited by other anti-β1 mAb as well as by anti-α4 mAb. Interestingly, anti-β1 mAb which induced strong aggregation of VLA-α2- or VLA-α4-transfected K562 cells, had minimal effect on the α2− α4− α5+ K562 cell line. Furthermore, the β1-mediated induction of cell aggregation on α2-K562- and α4-K562-transfected cells was blocked by preincubation with either anti-α2 or anti-α4 mAb, respectively, as well as by other anti-β1 mAb. Interestingly, parental K562 cells were able to interact with both α2- and α4-transfected K562 cells, thus suggesting that counter-receptors for both integrins (VLA-2 and VLA-4) might exist on these cells. Together these results provide strong evidence supporting the involvement of α2/β1 and α4/β1 heterodimers in intercellular interactions and underline the pivotal role of the common β1 chain of VLA proteins in the integrin-mediated induction of cell aggregation.

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