Plasminogen activator system in pemphigus vulgaris

Pemphigus vulgaris (PV) is caused by autoantibodies against desmosomes and is characterized by intra-epidermal blisters, The pathology of PV has been linked with plasminogen activation in lesional epidermis, The plasminogen activator system (PA system) consists of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA), as well as the two types of plasminogen activator inhibitors (PAI-1 and PAI-2). In keratinocytes, uPA binds to a specific cell surface receptor for uPA (uPA-R = CD87) in an autocrine manner. Cell-bound uPA is regulated by PAIs, The central PA system component plasminogen, which is present in plasma and interstitial fluids, is bound to the keratinocyte surface via plasmin(ogen) binding sites, where it can be activated by uPA-R-bound uPA. Cell surface-associated plasmin then mediates pericellular proteolysis. As the topographical organization of the distinct PA system components in lesional epidermis of PV remained elusive, we have performed the present immunohistological analysis of lesional and non-lesional epidermis of PV, In keratinocytes directly involved in the epidermal split formation, plasmin(ogen) was stained in nine of 10 cases, uPA-R and uPA in four of 10 cases and PAI-2 in seven of 10 cases. Together, acantholytic plasmin(ogen)(+) keratinocytes appeared in three different phenotypes: uPA-R(+)/uPA(+) and PAI-2(+), uPA-R(-)/uPA(-) and PAI-2(+), as well as uPA-R(-)/uPA(-) and PAI-2(-). Our findings demonstrate that, in acantholytic keratinocytes of PV, PAs and PAIs appear as differentially regulated components of the PA system.