Salmela M T, Pender S L, Reunala T, MacDonald T, Saarialho-Kere U
Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland.
Gut. 2001 Apr;48(4):496-502. doi: 10.1136/gut.48.4.496.
Dermatitis herpetiformis (DH) is a specific dermatological manifestation of coeliac disease and 80% of DH patients have gluten sensitive enteropathy manifested by crypt hyperplasia and villous atrophy. Matrix degradation mediated by collagenase 1 (MMP-1) and stromelysin 1 (MMP-3) has previously been implicated in the pathobiology of coeliac intestine and cutaneous DH blisters.
To study expression of stromelysin 2, metalloelastase, collagenase 3, and matrilysin in the intestine and skin of DH patients.
In situ hybridisation using 35S labelled cRNA probes was performed on duodenal biopsies of 15 DH patients, three samples each of control duodenal or jejunal mucosa, fetal ileal explants, lesional DH skin, and 19 serial biopsies of experimental DH blisters. Immunostaining was used to examine type IV collagen, macrophages (CD68), and 92 kDa gelatinase (MMP-9) in the specimens.
Metalloelastase (MMP-12) was abundantly expressed by subepithelial macrophages in both coeliac intestine and spontaneous and induced DH rash. It was also upregulated in the experimental model of coeliac disease (staphylococcal endotoxin B stimulated fetal explants). The only other MMP detected was MMP-9 which did not colocalise with MMP-12.
Upregulation of metalloelastase is associated with T cell mediated immune responses both in the intestine and skin. In addition to modulating macrophage migration, it may contribute to degradation of proteoglycans or basement membrane components in the subepithelial mucosa.
疱疹样皮炎（DH）是乳糜泻的一种特殊皮肤表现，80%的DH患者有麸质敏感性肠病，表现为隐窝增生和绒毛萎缩。先前已表明，由胶原酶1（基质金属蛋白酶-1，MMP-1）和基质溶解素1（MMP-3）介导的基质降解与乳糜泻肠道和皮肤DH水疱的病理生物学有关。
研究基质溶解素2、金属弹性蛋白酶、胶原酶3和基质溶素在DH患者肠道和皮肤中的表达。
使用35S标记的cRNA探针，对15例DH患者的十二指肠活检标本、对照十二指肠或空肠黏膜各3份样本、胎儿回肠外植体、DH皮损以及19份实验性DH水疱的连续活检标本进行原位杂交。采用免疫染色检查标本中的IV型胶原、巨噬细胞（CD68）和92 kDa明胶酶（MMP-9）。
金属弹性蛋白酶（MMP-12）在乳糜泻肠道以及自发性和诱发性DH皮疹的上皮下巨噬细胞中大量表达。在乳糜泻实验模型（葡萄球菌内毒素B刺激的胎儿外植体）中其表达也上调。检测到的唯一其他基质金属蛋白酶是MMP-9，其与MMP-12不共定位。
金属弹性蛋白酶的上调与肠道和皮肤中T细胞介导的免疫反应相关。除了调节巨噬细胞迁移外，它可能有助于上皮下黏膜中蛋白聚糖或基底膜成分的降解。
