Rieg Siegbert, Steffen Heiko, Seeber Silke, Humeny Andreas, Kalbacher Hubert, Dietz Klaus, Garbe Claus, Schittek Birgit
Department of Dermatology, Eberhard Karls University, Tubingen, Germany.
J Immunol. 2005 Jun 15;174(12):8003-10. doi: 10.4049/jimmunol.174.12.8003.
Antimicrobial peptides are an integral part of the epithelial innate defense system. Dermcidin (DCD) is a recently discovered antimicrobial peptide with a broad spectrum of activity. It is constitutively expressed in human eccrine sweat glands and secreted into sweat. Patients with atopic dermatitis (AD) have recurrent bacterial or viral skin infections and pronounced colonization with Staphylococcus aureus. We hypothesized that patients with AD have a reduced amount of DCD peptides in sweat contributing to the compromised constitutive innate skin defense. Therefore, we performed semiquantitative and quantitative analyses of DCD peptides in sweat of AD patients and healthy subjects using surface-enhanced laser desorption ionization time-of-flight mass spectrometry and ELISA. The data indicate that the amount of several DCD-derived peptides in sweat of patients with AD is significantly reduced. Furthermore, compared with atopic patients without previous infectious complications, AD patients with a history of bacterial and viral skin infections were found to have significantly less DCD-1 and DCD-1L in their sweat. To analyze whether the reduced amount of DCD in sweat of AD patients correlates with a decreased innate defense, we determined the antimicrobial activity of sweat in vivo. We showed that in healthy subjects, sweating leads to a reduction of viable bacteria on the skin surface, but this does not occur in patients with AD. These data indicate that reduced expression of DCD in sweat of patients with AD may contribute to the high susceptibility of these patients to skin infections and altered skin colonization.
抗菌肽是上皮先天性防御系统的一个组成部分。皮肤杀菌肽(DCD)是最近发现的一种具有广泛活性的抗菌肽。它在人类小汗腺中组成性表达并分泌到汗液中。特应性皮炎(AD)患者会反复出现细菌或病毒皮肤感染,且金黄色葡萄球菌定植明显。我们推测,AD患者汗液中DCD肽的含量降低,导致先天性皮肤防御能力受损。因此,我们使用表面增强激光解吸电离飞行时间质谱和酶联免疫吸附测定法,对AD患者和健康受试者汗液中的DCD肽进行了半定量和定量分析。数据表明,AD患者汗液中几种DCD衍生肽的含量显著降低。此外,与既往无感染并发症的特应性患者相比,有细菌和病毒皮肤感染史的AD患者汗液中的DCD-1和DCD-1L明显更少。为了分析AD患者汗液中DCD含量的降低是否与先天性防御能力下降相关,我们在体内测定了汗液的抗菌活性。我们发现,在健康受试者中,出汗会导致皮肤表面活菌数量减少,但在AD患者中则不会。这些数据表明,AD患者汗液中DCD表达降低可能导致这些患者对皮肤感染的高易感性以及皮肤定植改变。