Plasminogen activation in lesional skin of Pemphigus vulgaris type Neumann

Abstract

Zymographic and immunological studies revealed that primarily tissue-type plasminogen activator and to a lesser extent urokinase-type plasminogen activator were present in fluids of pemphigus vulgaris (type Neumann) skin blisters. Furthermore, plasmin activity was detected in pemphigus blister fluids using chromogenic peptide substrate assays. In pemphigus, but not in control, suction blister fluids plasmin/alpha 2-antiplasmin and plasmin/alpha 2-macroglobulin complexes were found by immunoprecipitation or by testing in immunoassays after fractionation by molecular-sieve chromatography. Plasmin activity, detected by a low molecular weight chromogenic peptide assay, was ascribed to plasmin/alpha 2-macroglobulin complexes. Since formation of plasmin/inhibitor complexes requires active plasmin, the finding indicates previous activation of plasminogen in pemphigus lesions.

Interleukin-1β upregulates tissue-type plasminogen activator in a keratinocyte cell line (HaCaT)

“…In contrast, tPA-specific mRNA [1], and tPA activity [22,33] and/or tPA-specific immunostaining [16,18,34] have been observed in lesional epidermis from patients with psoriasis, pemphigus foliaceus, pemphigus vulgaris, bullous pemphigoid and benign chronic pemphigus.…”

Increased activity of plasma and tissue kallikreins, plasma kininase II and salivary kallikrein in pemphigus foliaceus (fogo selvagem)

“…These findings suggest that the salivary glands more than the kidneys may be relevant sources of tissue kallikrein activation or production in PF. Blister lesions are not observed in the oral mucosa of PF patients; however, autoantibodies against desmoglein‐1 have been detected by indirect immunofluorescence in the oral mucosa of patients with this bullous dermatosis 14,40 , 44,45 . Whether the activation of salivary kallikrein is mediated by autoantibodies acting locally, or via systemic mediators reaching the salivary glands, are questions that need further clarification.…”

“…The involvement of the fibrinolytic system has been implicated in the pathogenesis of acantholysis in pemphigus. Previous studies have indicated that acantholysis depends on the activity of the UK‐type plasminogen activator 23–25,39 , 40 . In contrast, Mahoney et al 41 .…”

“…Previous studies have indicated that acantholysis depends on the activity of the UK-type plasminogen activator. [23][24][25]39,40 In contrast, Mahoney et al 41 reported that plasminogen activator knockout mice developed blister lesions after the injection of pemphigus vulgaris or PF serum. Recently, the production of IL-1a, TNF-a and UK plasminogen activator was associated with acantholysis in normal human keratinocytes incubated with pemphigus vulgaris serum.…”

A Possible Mechanism for Phenol‐Induced Pemphigus

“…The binding of PV IgG was found to increase the synthesis of PA 15 . Circulating plasminogen is bound to the keratinocytes at specific sites where it is converted to plasmin, which is thought to disrupt intercellular adhesion molecules, resulting in acantholysis 16 .…”