DIFFERENTIAL EXPRESSION OF ACTIVATION EPITOPES OF BETA-1 INTEGRINS INPSORIASIS AND NORMAL SKIN

In the epidermis, beta 1 integrin expression is normally confined to t he basal layer; however, suprabasal expression of beta 1 integrins in keratinocytes has been found in psoriasis, and it has been suggested t hat it could be a pathogenic factor of the disease. We have investigat ed herein the functional state of beta 1 integrins of human keratinocy tes in normal skin and psoriasis. The expression of beta 1-activation- reporter epitopes was monitored with two monoclonal antibodies, HUTS-2 1 and MG5A7, that recognize epitopes whose expression parallels functi onal activity of beta 1 integrins and correlates with the ligand bindi ng activity of these heterodimeric glycoproteins. We have found that k eratinocytes express activation epitopes of beta 1 integrins, and that these epitopes can be modulated by manganese. The expression of activ ation epitopes of beta 1 integrins was related to an enhanced adhesion to fibronectin and collagen. Immunohistochemical studies of normal an d psoriatic skin with HUTS-21 and other monoclonal antibodies indicate that, although there is suprabasal expression of beta 1 integrins in psoriasis, these molecules seem to be in an inactive state. Moreover, most beta 1 integrins in lateral and apical surfaces of basal keratino cytes of psoriasis are also in a nonactive conformation, implying a de crease of activity compared with normal skin, in which active beta 1 i ntegrins are distributed all over the basal keratinocytes.