Alessandrini F, Stachowitz S, Ring J, Behrendt H
Division of Environmental Dermatology and Allergy, GSF Research Center for Environment and Health/Technical University Munich, Munich, Germany.
J Invest Dermatol. 2001 Mar;116(3):394-400. doi: 10.1046/j.1523-1747.2001.01283.x.
Ceramides are the most abundant lipids constituting the intercellular matrix of the skin stratum corneum and their critical role in skin homeostasis has been extensively documented. Their concentration in the skin highly depends on the rate of availability of the enzymes involved in ceramide generation. The aim of this study was to investigate whether the concentration of prosaposin was altered in the skin of patients with psoriasis vulgaris. Prosaposin, the precursor of saposins (sphingolipid activator proteins), was measured in lesional and nonlesional skin of psoriatic patients and in normal skin from surgical patients, both at the mRNA and at the protein level. Densitometric analysis of reverse transcriptase-polymerase chain reaction bands separated by gel-electrophoresis showed a progressive decrease of prosaposin mRNA expression in nonlesional and lesional psoriatic skin, being substantially decreased in lesional psoriatic skin compared with normal control skin. Immunohistochemical analysis showed a significant decrease of prosaposin level in the stratum corneum of psoriatic lesional skin (both in active-type and in chronic-type plaque) compared with nonlesional and with normal skin (p < 0.01), and in psoriatic nonlesional skin compared with normal control (p < 0.05). Immunolocalization of sphingomyelinase in lesional and nonlesional psoriatic skin showed a decrease in the level of this enzyme in the stratum corneum of psoriatic lesional, compared with nonlesional skin. These results support the concept that disturbance of epidermal barrier function caused by derangement in ceramide generation can be crucial for the development of psoriatic skin diseases.
神经酰胺是构成皮肤角质层细胞间基质的最丰富脂质,其在皮肤稳态中的关键作用已得到广泛记载。它们在皮肤中的浓度高度依赖于参与神经酰胺生成的酶的可利用速率。本研究的目的是调查寻常型银屑病患者皮肤中鞘脂激活蛋白原的浓度是否发生改变。在银屑病患者的皮损和非皮损皮肤以及手术患者的正常皮肤中,均在mRNA和蛋白质水平上检测了鞘脂激活蛋白原(鞘脂激活蛋白的前体)。对凝胶电泳分离的逆转录酶 - 聚合酶链反应条带进行光密度分析显示,在银屑病非皮损和皮损皮肤中,鞘脂激活蛋白原mRNA表达逐渐降低,与正常对照皮肤相比,在银屑病皮损皮肤中显著降低。免疫组织化学分析显示,与非皮损和正常皮肤相比,银屑病皮损皮肤(包括活动型和慢性斑块型)角质层中的鞘脂激活蛋白原水平显著降低(p < 0.01),与正常对照相比,在银屑病非皮损皮肤中也降低(p < 0.05)。在银屑病皮损和非皮损皮肤中对鞘磷脂酶进行免疫定位显示,与非皮损皮肤相比,银屑病皮损角质层中该酶的水平降低。这些结果支持了这样一种观点,即神经酰胺生成紊乱导致的表皮屏障功能障碍可能对银屑病皮肤病的发展至关重要。