Differential expression of activation epitopes of beta1 integrins in psoriasis and normal skin.

In the epidermis, beta1 integrin expression is normally confined to the basal layer; however, suprabasal expression of beta1 integrins in keratinocytes has been found in psoriasis, and it has been suggested that it could be a pathogenic factor of the disease. We have investigated herein the functional state of beta1 integrins of human keratinocytes in normal skin and psoriasis. The expression of beta1-activation-reporter epitopes was monitored with two monoclonal antibodies, HUTS-21 and MG5A7, that recognize epitopes whose expression parallels functional activity of beta1 integrins and correlates with the ligand binding activity of these heterodimeric glycoproteins. We have found that keratinocytes express activation epitopes of beta1 integrins, and that these epitopes can be modulated by manganese. The expression of activation epitopes of beta1 integrins was related to an enhanced adhesion to fibronectin and collagen. Immunohistochemical studies of normal and psoriatic skin with HUTS-21 and other monoclonal antibodies indicate that, although there is suprabasal expression of beta1 integrins in psoriasis, these molecules seem to be in an inactive state. Moreover, most beta1 integrins in lateral and apical surfaces of basal keratinocytes of psoriasis are also in a nonactive conformation, implying a decrease of activity compared with normal skin, in which active beta1 integrins are distributed all over the basal keratinocytes.