92-KD GELATINASE IS PRODUCED BY EOSINOPHILS AT THE SITE OF BLISTER FORMATION IN BULLOUS PEMPHIGOID AND CLEAVES THE EXTRACELLULAR DOMAIN OF RECOMBINANT 180-KD BULLOUS PEMPHIGOID AUTOANTIGEN
92-KD GELATINASE IS PRODUCED BY EOSINOPHILS AT THE SITE OF BLISTER FORMATION IN BULLOUS PEMPHIGOID AND CLEAVES THE EXTRACELLULAR DOMAIN OF RECOMBINANT 180-KD BULLOUS PEMPHIGOID AUTOANTIGEN
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DOI：
10.1172/jci117196
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发表时间：
1994-05-01
影响因子：
15.9
通讯作者：
PARKS, WC
中科院分区：
文献类型：
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作者：
STAHLEBACKDAHL, M;INOUE, M;PARKS, WC
嗜酸性粒细胞在大疱性类天疱疮（BP）中非常突出，从这些细胞和其他炎症细胞分泌的蛋白酶可能导致基底膜的破坏。我们使用原位杂交和免疫组织化学方法定位了BP病变中92-kD明胶酶的表达位点。在所有样本（20/20）中，明胶酶mRNA的强烈信号仅在嗜酸性粒细胞中检测到，并且在这些细胞积聚在形成水泡的底部时最为明显。未见其他细胞酶mRNA阳性。然而，嗜酸性粒细胞和中性粒细胞都含有免疫反应性92-kD明胶酶，表明这种活性表达仅发生在嗜酸性粒细胞中。在水疱附近也可见脱颗粒的嗜酸性粒细胞，通过明胶酶谱、免疫印迹和酶联免疫吸附试验表明，92-kD明胶酶蛋白在BP水疱液中显著存在。在BP液中没有特异性检测到其他明胶溶解活性，在吸疱液中仅存在少量92-kD明胶酶。体外实验表明，92-kD明胶酶可切割重组180-kD BP自身抗原（BP180、BPAG2、HD4、XVII型胶原）的细胞外胶原结构域，这是一种表皮半脂体的跨膜分子。我们的研究结果表明，嗜酸性粒细胞产生和释放92-kD明胶酶对BP的组织损伤有重要作用。
Eosinophils are prominent in bullous pemphigoid (BP), and proteases secreted from these and other inflammatory cells may induce disruption of the basement membrane. We used in situ hybridization and immunohistochemistry to localize the sites of 92-kD gelatinase expression in BP lesions. In all samples (20/20), a strong signal for gelatinase mRNA was detected only in eosinophils and was most pronounced where these cells accumulated at the floor of forming blisters. No other cells were positive for enzyme mRNA. Both eosinophils and neutrophils, however, contained immunoreactive 92-kD gelatinase indicating that active expression occurred only in eosinophils. Degranulated eosinophils were also seen near blisters, and as demonstrated by gelatin zymography, immunoblotting, and ELISA, 92-kD gelatinase protein was prominent in BP blister fluid. No other gelatinolytic activity was specifically detected in BP fluid, and only small amounts of 92-kD gelatinase were present in suction blister fluids. As demonstrated in vitro, 92-kD gelatinase cleaved the extracellular, collagenous domain of recombinant 180-kD BP autoantigen (BP180, BPAG2, HD4, type XVII collagen), a transmembrane molecule of the epidermal hemidesmosome. Our results suggest that production and release 92-kD gelatinase by eosinophils contributes significantly to tissue damage in BP.