Plasminogen activator inhibitor type-2 in the lesional epidermis of lupus erythematosus

Under certain pathophysiological conditions epidermal keratinocytes produce urokinase-type plasminogen activator (LIPA) or tissue-type PA (tPA). These PAs are subject to regulation by PA inhibitors (PAI). including PAl type-2 (PAI-2). In the normal epidermis. PAI-2 is present in the differentiating suprabasal layers, albeit in the apparent absence of PAs. It has, therefore, been suggested that PAI-2 plays a role in epidermal differentiation not linked to its ability lo inhibit PAs. In line with this hypothesis, we have studied, by immunohistochemistry. the distribution of PAI-2. uPA and tPA in the normal and in the lesional epidermis of patients with lupus erythematosus (LE). a disease in which epidermal differentiation is disturbed. The PAI-2 antigen was detectable in the normal epidermis and in the lesional epidermis of LE. In the normal epidermis, the PAI-2 antigen was most pronounced in the granular layer. In the hyperkeratotic epidermal lesions of LE. the PAI-2 antigen was increased. In normal and lesional skin. PAI-2 was distributed along the cell periphery. Indicating its association with the cornified envelope. Neither uPA nor tPA was detectable in normal or lesional epidermis. Our findings show that PAI-2 is a major type of PAI in normal epidermis and in the lesional epidermis of LE, and that increased epidermal PAI-2 is observed in a disease which is not associated with an increase in epidermal PAs. The data support the hypothesis that epidermal PAI-2 may have other functions than the regulation of PA activity.