INCREASED EXPRESSION OF VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) IN BULLOUS PEMPHIGOID, DERMATITIS-HERPETIFORMIS, AND ERYTHEMA MULTIFORME

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the increased vascul ar permeability and angiogenesis associated with many malignant tumors , In addition, VPF/VEGF is strongly expressed by epidermal keratinocyt es in wound healing and psoriasis, disorders that are also characteriz ed by increased microvascular permeability and angiogenesis, In this s tudy, we investigated the expression of VPF/VEGF in three bullous dise ases with subepidermal blister formation that are characterized by hyp erpermeable dermal microvessels and pronounced papillary dermal edema, The expression of VPF/VEGF mRNA was strongly up-regulated in the lesi onal epidermis of bullous pemphigoid (n = 3), erythema multiforme (n = 3), and dermatitis herpetiformis (n = 4) as detected by in situ hybri dization, Epidermal labeling was particularly intense over blisters, b ut strong expression was also noted in areas of the epidermis adjacent to dermal inflammatory infiltrates at a distance from blisters, Moreo ver, the VPF/VEGF receptors, flt-1 and KDR, were up-regulated in endot helial cells in superficial dermal microvessels. High levels of VPF/VE GF (138-238 pM) were detected in blister fluids obtained from five pat ients with bullous pemphigoid, Addition of blister fluid to human derm al microvascular endothelial cells exerted a dose-dependent mitogenic effect that was suppressed after depletion of VPF/VEGF by immunoadsorp tion. These findings strongly suggest that VPF/VEGF plays an important role in the induction of increased microvascular permeability in bull ous diseases, leading to papillary edema and fibrin deposition and con tributing to the bulla formation characteristic of these disorders.