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经皮应用金黄色葡萄球菌肽聚糖可诱导小鼠皮肤嗜酸性粒细胞浸润。

Percutaneous application of peptidoglycan from Staphylococcus aureus induces eosinophil infiltration in mouse skin.

作者信息

Matsui K, Wirotesangthong M, Nishikawa A

机构信息

Department of Immunobiology, Meiji Pharmaceutical University, Tokyo, Japan.

出版信息

Clin Exp Allergy. 2007 Apr;37(4):615-22. doi: 10.1111/j.1365-2222.2007.02673.x.

Abstract

BACKGROUND

Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. The lesioned skin of AD patients shows an increased number of inflammatory cells such as eosinophils, mast cells and mononuclear cells in the dermis and superficial Staphylococcus aureus colonization.

OBJECTIVE

The purpose of this study was to determine the effects of peptidoglycan (PEG) from S. aureus on eosinophil induction in murine skin.

METHODS

PEG was applied to the barrier-disrupted abdominal skin of mice every 5 days. Twenty days later, the number of eosinophils in the abdominal skin was counted. The cytokine response in the skin was investigated by RT-PCR and immunohistological analysis. The regulated-upon activation in normal T cells expressed and secreted (RANTES) production from cultured epidermal cells was measured by ELISA.

RESULTS

The skin of mice treated with PEG showed a significantly increased number of eosinophils compared with that of mice treated with vehicle alone. In addition, application of PEG to the abdominal skin of mice increased the expression of mRNA for RANTES, but not that of mRNA for eotaxin, eotaxin-2 and monocyte chemotactic protein-3 in the skin. Immunohistologic analysis demonstrated that the levels of RANTES transcripts corresponded with those of protein synthesis in the epidermis. In vitro experiments using epidermal Langerhans cells (LCs) and keratinocytes (KCs) showed that RANTES production was induced by LCs but not by KCs stimulated with PEG. Furthermore, an intraperitoneal injection of anti-RANTES antibody neutralized the induction of eosinophils in the skin.

CONCLUSION

These results suggest that PEG may have an ability to induce eosinophil infiltration in the skin through RANTES production by LCs, and would explain the role of S. aureus colonization in AD patients.

摘要

背景

特应性皮炎(AD)是一种慢性炎症性皮肤病,其免疫病理特征因皮损持续时间而异。AD患者的皮损皮肤在真皮层显示嗜酸性粒细胞、肥大细胞和单核细胞等炎症细胞数量增加,且有表皮葡萄球菌定植。

目的

本研究旨在确定金黄色葡萄球菌肽聚糖(PEG)对小鼠皮肤中嗜酸性粒细胞诱导的影响。

方法

每5天对屏障破坏的小鼠腹部皮肤应用PEG。20天后,计数腹部皮肤中嗜酸性粒细胞的数量。通过逆转录聚合酶链反应(RT-PCR)和免疫组织学分析研究皮肤中的细胞因子反应。采用酶联免疫吸附测定(ELISA)法检测培养的表皮细胞中正常T细胞表达和分泌的调节激活正常T细胞表达和分泌因子(RANTES)的产生。

结果

与仅用赋形剂处理的小鼠相比,用PEG处理的小鼠皮肤中嗜酸性粒细胞数量显著增加。此外,对小鼠腹部皮肤应用PEG可增加皮肤中RANTES的mRNA表达,但不增加嗜酸性粒细胞趋化因子、嗜酸性粒细胞趋化因子-2和单核细胞趋化蛋白-3的mRNA表达。免疫组织学分析表明,RANTES转录水平与表皮中蛋白质合成水平相对应。使用表皮朗格汉斯细胞(LCs)和角质形成细胞(KCs)的体外实验表明,RANTES的产生是由LCs诱导的,而不是由PEG刺激的KCs诱导的。此外,腹腔注射抗RANTES抗体可中和皮肤中嗜酸性粒细胞的诱导。

结论

这些结果表明,PEG可能具有通过LCs产生RANTES诱导皮肤嗜酸性粒细胞浸润的能力,这可以解释金黄色葡萄球菌定植在AD患者中的作用。

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