DEGRADATION OF THE EPIDERMAL-DERMAL JUNCTION BY PROTEOLYTIC-ENZYMES FROM HUMAN-SKIN AND HUMAN POLYMORPHONUCLEAR LEUKOCYTES
DEGRADATION OF THE EPIDERMAL-DERMAL JUNCTION BY PROTEOLYTIC-ENZYMES FROM HUMAN-SKIN AND HUMAN POLYMORPHONUCLEAR LEUKOCYTES
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DOI：
10.1084/jem.160.4.1027
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发表时间：
1984-01-01
影响因子：
15.3
通讯作者：
LAZARUS, GS
中科院分区：
文献类型：
--
作者：
BRIGGAMAN, RA;SCHECHTER, NM;LAZARUS, GS
研究了人多形核白细胞蛋白水解酶天冬氨酸G和弹性蛋白酶，以及肥大细胞组成的人皮肤类糜蛋白酶对正常皮肤的降解作用。酶与新鲜的中厚皮肤孵育长达8小时；利用已知基底膜成分的抗体对组织进行超微结构和免疫组织化学检查。在所有病例中，观察到的主要损害发生在表皮-真皮交界处。弹性酶降解致密层，留下散乱的锚定纤维、真皮微纤维束和看起来正常的胶原纤维。免疫组织化学染色未见IV型胶原、层粘连蛋白、Kf1抗原和EBA抗原。大疱性类天疱疮抗原存在并定位于基底细胞。由类糜蛋白酶、组织蛋白酶G和人皮肤蛋白水解酶产生的表皮-真皮分离仅限于透明层。致密层和致密层下层纤维网络保持完好。人皮肤类凝乳蛋白酶能产生广泛的表皮-真皮分离，而组织蛋白酶G，在类似浓度下，只产生局部分离。免疫组织化学显示，与酶孵育后，所有抗原均存在。大疱性类天疱疮抗原位于裂开的表皮侧，层粘连蛋白位于真皮侧。表皮-真皮交界处对肥大细胞和多形核白细胞中的中性丝氨酸蛋白酶高度敏感。虽然所有的蛋白酶都会产生表皮-真皮分离，但降解的方式和程度是不同的。这种独特的降解模式可能为这些蛋白在皮肤病中的作用提供线索。
The degradation of normal human skin by the human polymorphonuclear leukocyte proteinases cathespin G and elastase, and by a human skin chymotrypsin-like proteinase that appears to be a mast cell constituent, was examined. Enzymes were incubated with fresh, split-thickness skin for up to 8 h; the tissue was examined ultrastructurally and immunohistochemically using antibodies to known basement membrane constituents. In all cases, the primary damage observed was at the epidermal-dermal junction. Elastase degraded the lamina densa leaving scattered and disorganized anchoring fibrils, dermal microfibril bundles and normal-appearing collagen fibers. Immunohistochemically, type IV collagen, laminin, KF1 and antigen and EBA antigen were absent. The bullous pemphigoid antigen was present and localized on the basal cells. Epidermal-dermal separation produced by the chymotrypsin-like proteinases, cathepsin G and the human skin proteinase, was confined to the lamina lucida. The lamina densa and sub-lamina densa fibrillar network remained intact. The human skin chymotrypsin-like proteinase produced extensive epidermal-dermal separation, while cathepsin G, at comparable concentrations, produced only focal separations. Immunohistochemically, all antigens were present after incubation with enzyme. The bullous pemphigoid antigen was found on the epidermal side of the split, while laminin was found on the dermal side. The epidermal-dermal junction is highly susceptible to neutral serine proteinases located in mast cells and polymorphonuclear leukocytes. Although all the proteinases produce epidermal-dermal separation, the patterns and extent of degradation are different. The distinctive patterns of degradation may provide a clue to the involvement of these proteinases in skin diseases.