Keratinocytes store the antimicrobial peptide cathelicidin in lamellar bodies
Keratinocytes store the antimicrobial peptide cathelicidin in lamellar bodies
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DOI：
10.1111/j.0022-202x.2004.23443.x
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发表时间：
2005-02-01
影响因子：
6.5
通讯作者：
Gallo, RL
中科院分区：
文献类型：
--
作者：
Braff, MH;Di Nardo, A;Gallo, RL
针对微生物病原体的先天免疫防御是通过物理屏障、中性粒细胞、NK细胞和巨噬细胞等细胞的募集以及具有抗菌活性的分子的分泌来实现的。这些分子是由包括皮肤在内的各种上皮细胞产生的。抗菌肽的重要性已经在肠道毒素缺乏的小鼠中得到证明，这种小鼠增加了皮肤对链球菌感染的易感性。尽管角质形成细胞在损伤后增加了天冬氨酸的表达，但它们相对于中性粒细胞天冬氨酸的作用以及它们的肽储存和激活位置还没有被阐明。本文报道了放线菌素主要存在于表浅表皮颗粒中，免疫金电子显微镜和免疫印迹法检测到部分分布于板层小体。在培养的角质形成细胞中，长春花碱呈颗粒状分布，部分定位于高尔基体内。免疫印迹分析可以在角质形成细胞提取液中观察到长春花素的加工过程，但在条件培养液中没有观察到。此外，荧光细菌与长春新碱在细胞内和细胞表面的颗粒中共存。这些观察显示了角质形成细胞通过抗菌肽的储存和处理直接作用的免疫防御潜力。
Innate immune defense against microbial pathogens occurs by physical barriers, by recruitment of cells such as neutrophils, NK cells, and macrophages, and by secretion of molecules with antimicrobial activity. Such molecules are produced by various epithelia including skin. The importance of antimicrobial peptides has been shown in cathelicidin-deficient mice, which have increased susceptibility to skin infection by Streptococcus. Although keratinocytes increase cathelicidin expression upon injury, their role relative to neutrophil cathelicidin and their sites of peptide storage and activation have not been elucidated. Herein, it is reported that cathelicidin predominantly resides in granules of the superficial epidermis and partially localizes in lamellar bodies as determined by immunogold electron microscopy and immunoblot of lamellar bodies isolated from mice. In cultured keratinocytes, cathelicidin displays a granular distribution and partially localizes within the Golgi apparatus. Cathelicidin processing can be observed by western blot analysis in keratinocyte extracts but not in conditioned media. Further, fluorescent bacteria colocalize with cathelicidin in granules both intracellularly and at the cell surface. These observations illustrate the immune defense potential of keratinocytes acting directly through storage and processing of antimicrobial peptides.