INCREASED EXPRESSION OF VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) IN BULLOUS PEMPHIGOID, DERMATITIS-HERPETIFORMIS, AND ERYTHEMA MULTIFORME
INCREASED EXPRESSION OF VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) IN BULLOUS PEMPHIGOID, DERMATITIS-HERPETIFORMIS, AND ERYTHEMA MULTIFORME
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DOI：
10.1111/1523-1747.ep12606974
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发表时间：
1995-05-01
影响因子：
6.5
通讯作者：
DETMAR, M
中科院分区：
文献类型：
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作者：
BROWN, LF;HARRIST, TJ;DETMAR, M
血管通透性因子（Vascular permeability factor， VPF），又称血管内皮生长因子（Vascular endothelial growth factor， VEGF），在许多恶性肿瘤的血管通透性增加和血管生成中起着重要作用。此外，在伤口愈合和银屑病等疾病中，表皮角质形成细胞强烈表达VPF/VEGF，这些疾病也以微血管通透性增加和血管生成为特征。我们研究了VPF/VEGF在三种以皮肤微血管高渗透和明显乳头状真皮水肿为特征的表皮下水疱形成的大疱性疾病中的表达，通过原位杂交检测，VPF/VEGF mRNA在大疱性类天疱疮（n = 3）、多形性红斑（n = 3）和疱疹样皮炎（n = 4）的病变表皮中表达强烈，表皮标记在水疱处特别强烈。此外，在皮肤浅层微血管内皮细胞中，VPF/VEGF受体flt-1和KDR表达上调。在5例大疱性类天疱疮患者的水疱液中检测到高水平的VPF/VEGF (138-238 pM)，在人皮肤微血管内皮细胞中添加水疱液具有剂量依赖性的有丝分裂效应，该效应在免疫吸附去除VPF/VEGF后被抑制。这些发现强烈提示VPF/VEGF在诱导大疱性疾病微血管通透性增加中起重要作用，导致乳头状水肿和纤维蛋白沉积，并促进这些疾病的大疱形成特征。
Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the increased vascular permeability and angiogenesis associated with many malignant tumors, In addition, VPF/VEGF is strongly expressed by epidermal keratinocytes in wound healing and psoriasis, disorders that are also characterized by increased microvascular permeability and angiogenesis, In this study, we investigated the expression of VPF/VEGF in three bullous diseases with subepidermal blister formation that are characterized by hyperpermeable dermal microvessels and pronounced papillary dermal edema, The expression of VPF/VEGF mRNA was strongly up-regulated in the lesional epidermis of bullous pemphigoid (n = 3), erythema multiforme (n = 3), and dermatitis herpetiformis (n = 4) as detected by in situ hybridization, Epidermal labeling was particularly intense over blisters, but strong expression was also noted in areas of the epidermis adjacent to dermal inflammatory infiltrates at a distance from blisters, Moreover, the VPF/VEGF receptors, flt-1 and KDR, were up-regulated in endothelial cells in superficial dermal microvessels. High levels of VPF/VEGF (138-238 pM) were detected in blister fluids obtained from five patients with bullous pemphigoid, Addition of blister fluid to human dermal microvascular endothelial cells exerted a dose-dependent mitogenic effect that was suppressed after depletion of VPF/VEGF by immunoadsorption. These findings strongly suggest that VPF/VEGF plays an important role in the induction of increased microvascular permeability in bullous diseases, leading to papillary edema and fibrin deposition and contributing to the bulla formation characteristic of these disorders.