Increased stratum corneum serine protease activity in acute eczematous atopic skin
Increased stratum corneum serine protease activity in acute eczematous atopic skin
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DOI：
10.1111/j.1365-2133.2009.09142.x
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发表时间：
2009-07-01
影响因子：
10.3
通讯作者：
Fluhr, J. W.
中科院分区：
文献类型：
--
作者：
Voegeli, R.;Rawlings, A. V.;Fluhr, J. W.
背景特应性皮炎（AD）是一种与角质层结构和功能改变相关的慢性炎症性疾病。AD中表皮屏障功能的破坏与角质细胞大小和成熟、脱屑、脂质分布和一些蛋白酶活性的变化有关。目的本研究的目的是：（i）检测急性湿疹性AD皮损（L）皮肤的生理变化，与非皮损（NL）AD皮肤和健康（H）皮肤进行比较，使用连续的Tewametry和SC蛋白分析来估计SC厚度;方法6例H型皮肤、6例NL型皮肤AD患者和6例轻中度湿疹（L型皮肤）AD患者均入选研究。皮肤评估使用几种非侵入性技术，但SC厚度估计使用tewametry和SC蛋白质含量的D-虾夷扇贝剥离。通过连续胶带剥离（D-Squame）和红外光密度测定法测定SC完整性。结果D-鳞状细胞剥脱术后，L皮肤的经皮水分损失（TEWL）水平在所有采样点均高于NL和H皮肤（P < 0.05）。相反，在L皮肤中，连续胶带剥离去除的SC量减少，表明角膜细胞内凝聚力增加（P < 0.05）。通过将1/TEWL值与去除的SC作为SC厚度的估计值相关联，与NL和H皮肤相比，在L中观察到显著更薄的SC（P < 0.05）。在AD皮肤中测量了升高的可提取丝氨酸蛋白酶活性，顺序为：SC类胰蛋白酶（45 x）、纤溶酶（30 x）、尿激酶（7.1 x）、胰蛋白酶样激肽释放酶（5.8 x）和胰凝乳蛋白酶样激肽释放酶（3.9 x）。在H和NL皮肤中未检测到白细胞弹性蛋白酶活性，但在AD SC样品（L皮肤）中观察到。与NL和HSC样品相比，所有酶在L SC的深层中升高。所有一贯升高的SC蛋白酶活性显着相关的bioinstrumentaldata.Conclusions我们报告增加丝氨酸蛋白酶活性在急性湿疹AD，特别是在更深层次的SC，包括SC类胰蛋白酶，纤溶酶，尿激酶和白细胞弹性蛋白酶的活动。这些蛋白酶活性的升高与屏障功能受损、刺激和皮肤电容降低有关。尽管胶带剥离期间TEWL升高，但SC凝聚力明显增加，这表明AD急性湿疹性病变中SC厚度降低。事实上，这是通过估计SC厚度观察到的。
Background Atopic dermatitis (AD) is a chronic inflammatory disease associated with changes in stratum corneum (SC) structure and function. The breakdown of epidermal barrier function in AD is associated with changes in corneocyte size and maturation, desquamation, lipid profiles, and some protease activities.Objectives The purpose of this study was: (i) to examine physiological changes in lesional (L) skin of acute eczematous AD, compared with nonlesional (NL) AD skin and healthy (H) skin, using sequential tewametry and SC protein analysis to estimate SC thickness; and (ii) to assess which serine proteases might be involved in pathogenesis.Methods Six subjects with H skin, six AD patients with NL skin and six AD patients with mild to moderate eczema (L skin) were enrolled. Skin was assessed using several noninvasive techniques but SC thickness was estimated using tewametry and SC protein content of D-Squame strippings. SC integrity was determined by sequential tape stripping (D-Squame) and infrared densitometry. Kallikreins, plasmin, urokinase and leucocyte elastase protease activities together with a novel SC tryptase-like enzyme activity were quantified.Results Transepidermal water loss (TEWL) levels after D-Squame stripping were elevated in L compared with NL and H skin at all sampling points (P < 0.05). Conversely, the amount of SC removed by sequential tape stripping was decreased in L skin, indicating increased intracorneocyte cohesion (P < 0.05). By correlating 1/TEWL values and SC removed as an estimate of SC thickness, a significantly thinner SC was observed in L compared with NL and H skin (P < 0.05). Elevated extractable serine protease activity was measured in AD skin in the order: SC tryptase-like enzyme (45x), plasmin (30x), urokinase (7.1x), trypsin-like kallikreins (5.8x) and chymotrypsin-like kallikreins (3.9x). Leucocyte elastase activity was not detected in H and NL skin but was observed in AD SC samples (L skin). All enzymes were elevated in the deeper layers of L SC compared with NL and H SC samples. All consistently elevated SC protease activities were significantly correlated with the bioinstrumental data.Conclusions We report increased serine protease activities in acute eczematous AD, especially in deeper layers of the SC, including SC tryptase-like enzyme, plasmin, urokinase and leucocyte elastase activities. These elevations in protease activities were associated with impaired barrier function, irritation, and reduced skin capacitance. Increased SC cohesion was apparent despite elevated TEWL during tape stripping, which would indicate reduced SC thickness in acute eczematous lesions of AD. Indeed, this was observed using an estimate of SC thickness.