Vaalamo M, Kariniemi A L, Shapiro S D, Saarialho-Kere U
Department of Dermatology, Helsinki University Central Hospital, Finland.
J Invest Dermatol. 1999 Apr;112(4):499-505. doi: 10.1046/j.1523-1747.1999.00547.x.
Accumulation of inflammatory cells such as macrophages may lead to degeneration of connective tissue matrix in various skin diseases. Macrophage metalloelastase, is a matrix metalloproteinase (MMP-12) capable of degrading elastin as well as various basement membrane components. To investigate the role of human macrophage metalloelastase in skin, we assessed by in situ hybridization and immunohistochemistry 66 specimens representing skin diseases characterized either by changes in elastic fibers or by pronounced infiltrations of extravasating and migrating macrophages. CD68 immunostaining was performed to identify the human macrophage metalloelastase-positive cells and Weigert's Resorcin-Fuchsin staining to reveal the status of elastic fibers. We found abundant expression of human macrophage metalloelastase mRNA in macrophages in areas devoid of normal elastic fibers in granulomatous skin diseases sarcoidosis, necrobiosis lipoidica diabeticorum, and granuloma annulare. Positive cells for human macrophage metalloelastase protein could be detected in the same regions as well as positive immunostaining for urokinase plasminogen activator. Of the other matrix metalloproteinases capable of degrading elastin, 92 kDa gelatinase colocalized with human macrophage metalloelastase, while 72 kDa gelatinase was produced by surrounding fibroblast-like cells. Furthermore, human macrophage metalloelastase was expressed by macrophages in areas with disrupted basement membrane, as assessed by type IV collagen staining, in pityriasis lichenoides and dermatitis herpetiformis. Specimens of anetoderma, acrodermatitis chronica atrophicans and pseudoxanthoma elasticum showed no signal for human macrophage metalloelastase. Matrilysin was not detected in any of the samples investigated. Our study suggests that human macrophage metalloelastase may contribute to elastin degradation occurring in granulomatous skin diseases and may aid macrophage migration through the epidermal and vascular basement membranes in inflammatory disorders.
巨噬细胞等炎症细胞的积聚可能导致多种皮肤疾病中结缔组织基质的退化。巨噬细胞金属弹性蛋白酶是一种基质金属蛋白酶（MMP - 12），能够降解弹性蛋白以及各种基底膜成分。为了研究人巨噬细胞金属弹性蛋白酶在皮肤中的作用，我们通过原位杂交和免疫组织化学对66份代表皮肤疾病的标本进行了评估，这些疾病的特征要么是弹性纤维的变化，要么是渗出和迁移的巨噬细胞的明显浸润。进行CD68免疫染色以鉴定人巨噬细胞金属弹性蛋白酶阳性细胞，并用魏格特氏间苯二酚品红染色来显示弹性纤维的状态。我们发现在肉芽肿性皮肤病结节病、糖尿病性类脂质渐进性坏死和环状肉芽肿中，在缺乏正常弹性纤维的区域，巨噬细胞中人巨噬细胞金属弹性蛋白酶mRNA表达丰富。在相同区域可检测到人巨噬细胞金属弹性蛋白酶蛋白的阳性细胞以及尿激酶型纤溶酶原激活剂的阳性免疫染色。在能够降解弹性蛋白的其他基质金属蛋白酶中，92 kDa明胶酶与人巨噬细胞金属弹性蛋白酶共定位，而72 kDa明胶酶由周围的成纤维细胞样细胞产生。此外，通过IV型胶原染色评估，在苔藓样糠疹和疱疹样皮炎中，基底膜破坏区域的巨噬细胞表达人巨噬细胞金属弹性蛋白酶。皮肤松弛症、慢性萎缩性肢端皮炎和弹性假黄瘤的标本未显示人巨噬细胞金属弹性蛋白酶信号。在所研究的任何样本中均未检测到基质溶素。我们的研究表明，人巨噬细胞金属弹性蛋白酶可能促成肉芽肿性皮肤病中发生的弹性蛋白降解，并可能有助于巨噬细胞在炎症性疾病中穿过表皮和血管基底膜迁移。
