Major role for neutrophils in experimental bullous pemphigoid
Major role for neutrophils in experimental bullous pemphigoid
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DOI：
10.1172/jci119639
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发表时间：
1997-09-01
影响因子：
15.9
通讯作者：
Diaz, LA
中科院分区：
文献类型：
--
作者：
Liu, Z;Giudice, GJ;Diaz, LA
大疱性类天疱疮（BP）是一种炎性表皮下水疱性疾病，与对半桥粒蛋白BP 180的IgG自身免疫应答相关。使用被动转移小鼠模型，我们的小组先前已经表明，针对鼠BP 180（mBP 180）胞外域的抗体能够触发与人BP非常相似的水疱性皮肤病。在这项研究中，我们研究了嗜中性粒细胞在该疾病模型的免疫发病机制中的作用，通过用嗜中性粒细胞特异性抗体处理而耗尽循环嗜中性粒细胞的BALB/c小鼠不再对抗mBP 180 IgG的致病作用敏感，IgG和补体沉积在这些动物的真皮-表皮连接处，但没有炎症浸润或水泡的迹象，CS缺陷小鼠？其对抗mBP 180 IgG的致病活性具有抗性，通过皮内施用嗜中性粒细胞化学引诱物IL-8或C5 α，可以使其对这种IgG介导的起泡疾病敏感。腹膜内注射IL-8，其在腹膜腔中隔离嗜中性粒细胞，干扰抗mBP 180诱导的皮肤嗜中性粒细胞浸润并防止BALB/c小鼠中BP疾病的发展，这些研究结果提供了第一个直接证据表明，通过CS依赖性途径招募到皮肤的中性粒细胞在实验性BP的表皮下水疱形成中发挥重要作用，并提出了疾病干预的新方向。
Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with an IgG autoimmune response to the hemidesmosomal protein, BP180, Using a passive transfer mouse model, our group has shown previously that antibodies to the murine BP180 (mBP180) ectodomain are capable of triggering a blistering skin disease that closely mimics human BP, In this study, we investigated the role of neutrophils in the immunopathogenesis of this disease model, BALB/c mice depleted of circulating neutrophils by treatment with neutrophil-specific antibodies were no longer susceptible to the pathogenic effects of anti-mBP180 IgG, IgG and complement were deposited at the dermal-epidermal junction of these animals, but there was no evidence of inflammatory infiltration or blistering, CS-deficient mice? which are resistant to the pathogenic activity of anti-mBP180 IgG, could be made susceptible to this IgG-mediated blistering disease by intradermal administration of a neutrophil chemoattractant, IL-8 or C5a, Intraperitoneal injection of IL-8, which sequesters neutrophils in the peritoneal cavity, interferes with anti-mBP180-induced neutrophilic infiltration of the skin and prevented the development of BP disease in BALB/c mice, These findings provide the first direct evidence that neutrophils recruited to the skin via a CS-dependent pathway play an essential role in subepidermal blister formation in experimental BP, and suggest new directions for disease intervention.