Bullous pemphigoid: using animal models to study the immunopathology.
Bullous pemphigoid: using animal models to study the immunopathology.
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大疱性类天疱疮：利用动物模型研究免疫病理学。
DOI：
10.1111/j.1087-0024.2004.00841.x
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Liu,Zhi
中科院分区：
文献类型：
--
作者：
Liu,Zhi
大疱性类天疱疮于1953年首次被Lever描述为一种表皮下水泡病。其免疫组织学特征包括真皮-表皮交界处分离，真皮上部炎性细胞浸润，基底膜带状自身抗体。这些自身抗体在真皮-表皮交界处呈线性染色，激活补体，识别两种主要的半染色体抗原，BP230(BPAG1)和BP180(BPAG2或XVI型胶原)。用兔抗尿BP180抗体免疫新生小鼠，建立BP免疫球蛋白被动转移小鼠模型。这个模型概括了人类大疱性天疱疮的主要特征。利用这个活体模型系统，我们确定了导致大疱性天疱疮表型的几个关键的细胞和分子事件，包括免疫球蛋白结合、补体激活、肥大细胞脱颗粒和中性粒细胞的渗透和激活。中性粒细胞释放的蛋白酶和活性氧共同作用破坏基底膜区，导致真皮-表皮连接分离。最近来自人类大疱性天疱疮研究的实验数据表明，人类大疱性天疱疮及其相应的小鼠免疫球蛋白被动转移模型可能不仅具有共同的免疫组织学特征，而且可能具有导致这种抗体介导疾病发生的病理机制。
Bullous pemphigoid was first described by Lever in 1953 as a subepidermal blistering disease. Its immunohistological features include dermal–epidermal junction separation, an inflammatory cell infiltrate in the upper dermis, and basement membrane zone–bound autoantibodies. These autoantibodies show a linear staining at the dermal–epidermal junction, activate complement, and recognize two major hemidesmosomal antigens, BP230 (BPAG1) and BP180 (BPAG2 or type XVII collagen). An IgG passive transfer mouse model of BP was developed by administering rabbit antimurine BP180 antibodies to neonatal mice. This model recapitulates the key features of human bullous pemphigus. Using thisin vivomodel system, several key cellular and molecular events leading to the bullous pemphigus disease phenotype were identified, including IgG binding, complement activation, mast cell degranulation, and neutrophil infiltration and activation. Proteinases and reactive oxygen species released by neutrophils work together to damage the basement membrane zone, causing dermal–epidermal junction separation. Recent experimental data from human bullous pemphigus studies suggest that human bullous pemphigus and its mouse IgG passive transfer model counterpart may well share not only common immunohistological features but also pathological mechanisms underlying the development of this antibody-mediated disease.