Narbutt Joanna, Waszczykowska Elzbieta, Lukamowicz Jolanta, Sysa-Jedrzejowska Anna, Kobos Józef, Zebrowska Agnieszka
Department of Dermatology and Venereology, Medical University of Lódź.
Pol J Pathol. 2006;57(2):71-6.
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease which pathogenesis is associated with destruction of the basement membrane components and the anchoring fibers. The binding of autoantibodies to antigens localized in the basement membrane of the epidermis activates a series of immunological and enzymatic phenomena that lead to blister formation. There are some data that MMPs are involved in the development of skin lesions in BP, however their exact role in this process is not fully understood. We aimed to investigate whether MMPs and their inhibitors (TIMPs), assessed by their tissue expression, are involved in the pathogenesis of BP. The localization and expression of collagenase (MMP1), gelatinase (MMP2), 92 kD gelatinase (MMP9) and stromelysin 2 (MMP10) and TIMP1, 2, 3 were examined by immunohistochemistry in skin biopsies as well as in normal human skin specimens. The study included 21 patients with BP at an active stage of the disease. The MMPs and TIMPs serum levels were measured by ELISA method. Expression of MMP1, MMP2, MMP9 and MMP10 was observed either in the whole epidermis or in the basal keratinocytes. Most of the enzymes examined, apart from TIMP3, were detected in dermal part of the blister. Expression of the majority of the enzymes examined was observed in blister fluid however, the most intense signal was noted for MMP10. In cellular infiltrate we found expression of all the MMPs and TIMPs, the most distinct for MMP1, MMP2, MMP10 and for TIMP2. In all biopsies obtained from healthy volunteers only single basal keratinocytes gave positive, weak signal for the examined proteins. The MMPs and TIMPs serum levels in the control group were normal while in some cases of BP patients they were increased. Based on the results we conclude that imbalance between these enzymes really occurs in BP and it is likely to take important part in the pathogenesis of the disease.
大疱性类天疱疮（BP）是一种自身免疫性表皮下大疱性疾病，其发病机制与基底膜成分和锚定纤维的破坏有关。自身抗体与位于表皮基底膜的抗原结合，激活一系列免疫和酶学现象，导致水疱形成。有一些数据表明基质金属蛋白酶（MMPs）参与了BP皮肤病变的发展，然而它们在这个过程中的确切作用尚未完全明确。我们旨在研究通过组织表达评估的MMPs及其抑制剂（TIMPs）是否参与BP的发病机制。通过免疫组织化学在皮肤活检标本以及正常人皮肤标本中检测胶原酶（MMP1）、明胶酶（MMP2）、92 kD明胶酶（MMP9）、基质溶解素2（MMP10）以及TIMP1、2、3的定位和表达。该研究纳入了21例处于疾病活动期的BP患者。采用酶联免疫吸附测定（ELISA）法测量MMPs和TIMPs的血清水平。观察到MMP1、MMP2、MMP9和MMP10在整个表皮或基底角质形成细胞中表达。除TIMP3外，大多数检测的酶在水疱的真皮部分被检测到。在水疱液中观察到大多数检测酶的表达，然而，MMP10的信号最强。在细胞浸润中，我们发现所有MMPs和TIMPs均有表达，其中MMP1、MMP2、MMP10和TIMP2最为明显。在所有取自健康志愿者的活检标本中，仅单个基底角质形成细胞对检测的蛋白质呈阳性、弱阳性信号。对照组中MMPs和TIMPs的血清水平正常，而在一些BP患者中升高。基于这些结果，我们得出结论，在BP中这些酶之间确实存在失衡，并且很可能在疾病的发病机制中起重要作用。
