INTERACTION OF INTEGRINS ALPHA-3-BETA-1 AND ALPHA-2-BETA-1 - POTENTIAL ROLE IN KERATINOCYTE INTERCELLULAR-ADHESION

The colocalization of integrins alpha2beta1 and alpha3beta1 at intercellular contact sites of keratinocytes in culture and in epidermis suggests that these integrins may mediate intercellular adhesion (ICA). PlB5, an anti-alpha3beta1 mAb previously reported to inhibit keratinocyte adhesion to epiligrin, was also found to induce ICA. Evidence that P1B5-induced ICA was mediated by alpha2beta1 and alpha3beta1 was obtained using both ICA assays and assays with purified, mAb-immobilized integrins. Selective binding of alpha2beta1-coated beads to epidermal cells or plate-bound alpha3beta1 was observed. This binding was inhibited by mAbs to integrin alpha3, alpha2, or beta1 subunits and could be stimulated by P1B5. We also demonstrate a selective and inhibitable interaction between affinity-purified integrins alpha2beta1 and alpha3beta1. Finally, we show that expression of alpha2beta1 by CHO fibroblasts results in the acquisition of collagen and alpha3beta1 binding. Binding to both of these ligands is inhibited by P1H5, an anti-alpha2beta1 specific mAb. Results of these in vitro experiments suggest that integrins alpha2beta1 and alpha3beta1 can interact and may do so to mediate ICA in vivo. Thus, alpha3beta1 mediates keratinocyte adhesion to epiligrin and plays a second role in ICA via alpha2beta1.