Beta 1 integrins do not have a major role in keratinocyte intercellular adhesion.

Integrins of the epidermis have been implicated both in intercellular adhesion and in cell-substratum adhesion. In the present study the role of alpha 2 beta 1 and alpha 3 beta 1 integrins has been evaluated further using human keratinocyte culture. alpha 3 beta 1 but not alpha 2 beta 1 strongly colocalizes with talin in adhesion plaques, consistent with a role for the former in adhesion to endogenous matrix. Upon elevation of the extracellular Ca2+ concentration from 30 microM to 1.0 mM, which is known to induce the organization of intercellular junctions, all three integrin subunits redistribute to concentrate along the cell-cell borders, but alpha 3 redistributes more slowly. Blocking antibody to E-cadherin, which has previously been shown to delay the establishment of cell-cell adhesion upon Ca2+ elevation, delays the redistribution of alpha 2 beta 1 and alpha 3 beta 1 integrins. Elevation of the Ca2+ concentration also induces a rapid morphological change in the keratinocytes and organization of the culture into colonies with tight cell-cell connections. Blocking antibodies to beta 1 or to alpha 3, but not to alpha 2, delays this morphological change and the organization into colonies; however, the effect is much more pronounced in subconfluent cultures. These data are consistent with the hypothesis that anti-beta 1 or anti-alpha 3 antibodies affect cell-cell interactions primarily through their previously described inhibition of motility. Stratification of the culture, which follows the formation of intercellular interactions, is normal in the presence of blocking antibody to beta 1 integrin. In summary, these data suggest that integrins do not play a major role in intercellular keratinocyte adhesion, but may appear to do so under certain conditions because of their involvement in motility.