Interaction of integrins α₃β₁ and α₂β₁: Potential role in keratinocyte intercellular adhesion

The colocalization of integrins α₂β₁ and α₃β₁ at intercellular contact sites of keratinocytes in culture and in epidermis suggests that these integrins may mediate intercellular adhesion (ICA). P1B5, an anti-α₃β₁ mAb previously reported to inhibit keratinocyte adhesion to epiligrin, was also found to induce ICA. Evidence that P1B5-induced ICA was mediated by α₂β₁ and α₃β₁ was obtained using both ICA assays and assays with purified, mAb-immobilized integrins. Selective binding of α₂β₁-coated beads to epidermal cells or plate-bound α₃β₁ was observed. This binding was inhibited by mAbs to integrin α₃, α₂, or β₁ subunits and could be stimulated by P1B5. We also demonstrate a selective and inhibitable interaction between affinity-purified integrins α₂β₁ and α₃β₁. Finally, we show that expression of α₂β₁ by CHO fibroblasts results in the acquisition of collagen and α₃β₁binding. Binding to both of these ligands is inhibited by P1H5, an anti-α₂β₁ specific mAb. Results of these in vitro experiments suggest that integrins α₂β₁ and α₃β₁ can interact and may do so to mediate ICA in vivo. Thus, α₃β₁ mediates keratinocyte adhesion to epiligrin and plays a second role in ICA via α₂β₁.