Department of Microbiology and Immunology, UC Davis School of Medicine, Davis, CA 95616-8645, USA.
J Innate Immun. 2012;4(3):248-59. doi: 10.1159/000334566. Epub 2012 Jan 19.
The skin functions as more than a physical barrier to infection. Epithelial cells of the skin can synthesize antimicrobial peptides, including defensins, which exhibit direct antimicrobial activity. Here we characterize the expression pattern, genetic variation and activity of the major β-defensin expressed in canine skin, canine β-defensin 103 (CBD103). The gene encoding CBD103 exhibits two forms of polymorphism: a common 3-basepair deletion allele and a gene copy-number variation. Golden retrievers and Labrador retrievers were the only breeds that encoded the variant allele of CBD103, termed CBD103ΔG23. Both these breeds also exhibited a CBD103 gene copy-number polymorphism that ranged from 2 to 4 gene-copies per diploid genome. Recombinant CBD103 and CBD103ΔG23, as well as the human ortholog human β-defensin 3 (hBD3) and hBD3ΔG23, showed potent and comparable antimicrobial killing against both methicillin-susceptible and methicillin-resistant Staphylococcus pseudintermedius. Skin biopsy specimens from dogs with atopic dermatitis revealed CBD103 expression levels similar to those in healthy controls and comparable at lesional and nonlesional sites. This expression pattern in dogs differs from the previously reported reduced expression of the human ortholog in atopic dermatitis. Overall, the similarities of CBD103 and its human ortholog reported here support the notion that the domestic dog may serve as a valuable model for studying β-defensin biology in the skin.
皮肤不仅是抵御感染的物理屏障。皮肤的上皮细胞可以合成抗菌肽,包括防御素,它们具有直接的抗菌活性。在这里,我们描述了犬皮肤中主要β-防御素犬β-防御素 103(CBD103)的表达模式、遗传变异和活性。编码 CBD103 的基因表现出两种形式的多态性:常见的 3 碱基对缺失等位基因和基因拷贝数变异。金毛寻回犬和拉布拉多寻回犬是唯一编码 CBD103 变异等位基因的品种,称为 CBD103ΔG23。这两个品种还表现出 CBD103 基因拷贝数多态性,每个二倍体基因组的基因拷贝数从 2 到 4 个不等。重组 CBD103 和 CBD103ΔG23 以及人同源物人β-防御素 3(hBD3)和 hBD3ΔG23 对甲氧西林敏感和耐甲氧西林金黄色葡萄球菌均显示出强大且相当的抗菌杀伤作用。特应性皮炎犬的皮肤活检标本显示 CBD103 的表达水平与健康对照组相似,且在病变和非病变部位相似。这种在犬中的表达模式与先前报道的人同源物在特应性皮炎中表达减少的情况不同。总体而言,这里报道的 CBD103 及其人同源物的相似性支持了这样一种观点,即家犬可能是研究皮肤中β-防御素生物学的有价值模型。