Complement and plasminogen: pathways in inflammation

The subepidermal blistering skin disease bullous pemphigoid is associated with the deposition of specific autoantibodies and activated complement at the epidermal basement membrane zone of lesional skin. Subepidermal blistering is thought to depend on proteolytic enzymes, in particular on plasmin. A possible interrelation is proposed between the initiating immune reaction and the plasminogen activator system. Complement-induced chemotaxis of PMN may induce PMN infiltration. PMN-derived reactive oxygen species would interfere with the plasminogen activator inhibitors. Lysosomal elastase may degrade alpha 2-antiplasmin. At the same time, urokinase-type plasminogen activator is stimulated in tissue constituent cells and plasmin activity increases locally. The plasmin/antiplasmin equilibrium is disturbed and excess plasmin, then, may cause the degradation of extracellular proteinaceous structures of the epidermo/dermal junction. Epidermo/dermal dyshesion and subepidermal blister formation ensues. The plasminogen activator system is seen as a part within the wide array of effector systems that may be operative upon stimulation by an initial immunological event.