Interaction of integrins alpha 3 beta 1 and alpha 2 beta 1: potential role in keratinocyte intercellular adhesion.
The colocalization of integrins alpha 2 beta 1 and alpha 3 beta 1 at intercellular contact sites of keratinocytes in culture and in epidermis suggests that these integrins may mediate intercellular adhesion (ICA). P1B5, an anti-alpha 3 beta 1 mAb previously reported to inhibit keratinocyte adhesion to epiligrin, was also found to induce ICA. Evidence that P1B5-induced ICA was mediated by alpha 2 beta 1 and alpha 3 beta 1 was obtained using both ICA assays and assays with purified, mAb-immobilized integrins. Selective binding of alpha 2 beta 1-coated beads to epidermal cells or plate-bound alpha 3 beta 1 was observed. This binding was inhibited by mAbs to integrin alpha 3, alpha 2, or beta 1 subunits and could be stimulated by P1B5. We also demonstrate a selective and inhibitable interaction between affinity-purified integrins alpha 2 beta 1 and alpha 3 beta 1. Finally, we show that expression of alpha 2 beta 1 by CHO fibroblasts results in the acquisition of collagen and alpha 3 beta 1 binding. Binding to both of these ligands is inhibited by P1H5, an anti-alpha 2 beta 1 specific mAb. Results of these in vitro experiments suggest that integrins alpha 2 beta 1 and alpha 3 beta 1 can interact and may do so to mediate ICA in vivo. Thus, alpha 3 beta 1 mediates keratinocyte adhesion to epiligrin and plays a second role in ICA via alpha 2 beta 1.
Symington
B E
BE
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Takada
Y
Y
Carter
W G
WG
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation; D002460:Cell Line; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D006224:Cricetinae; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D046911:Macromolecular Substances; D011994:Recombinant Proteins / Q000032:analysis / Q000378:metabolism; D014162:Transfection
D016023:Integrins; D046911:Macromolecular Substances; D011994:Recombinant Proteins