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新生儿受到一种先天性抗菌屏障的保护:皮肤和胎脂中存在肽抗生素。

The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa.

作者信息

Marchini G, Lindow S, Brismar H, Ståbi B, Berggren V, Ulfgren A-K, Lonne-Rahm S, Agerberth B, Gudmundsson G H

机构信息

Department of Woman and Child Health, Astrid Lindgren Children's Hospital, Karolinska Hospital C4:U1, Karolinska Institutet, S-171 76 Stockholm, Sweden.

出版信息

Br J Dermatol. 2002 Dec;147(6):1127-34. doi: 10.1046/j.1365-2133.2002.05014.x.

Abstract

BACKGROUND

Peptide antibiotics are part of the surface defences against microbial intruders. However, the presence and significance of these innate immune effectors in the skin barrier of the newborn infant have not yet been appreciated. Erythema toxicum neonatorum is an inflammatory skin reaction of unknown aetiology and significance, commonly present in the healthy newborn infant.

OBJECTIVES

As peptide antibiotics are upregulated in inflammatory skin disorders, we hypothesized that this also could be the case in erythema toxicum. We also investigated if the vernix caseosa, a cream-like white substance present on the skin of the infant at birth, might contribute to host defences.

METHODS

The presence of the human antibacterial peptide LL-37 was investigated by immunohistochemistry and confocal imaging of skin biopsies from four 1-day-old infants with an erythema toxicum rash and four matched newborns without the rash. In addition, we analysed the expression of LL-37 and human beta defensin-1, an antibacterial peptide of epithelial origin, by reverse transcriptase-polymerase chain reaction. Finally, we screened for antibacterial components in vernix material obtained from six healthy newborns by inhibition zone assays.

RESULTS

All biopsies from the lesions of erythema toxicum showed a dense, nodular infiltrate with numerous LL-37-expressing cells located in the dermal layer and a clear localization of the peptide within CD15-expressing neutrophils, EG2-expressing eosinophils and CD1a-expressing dendritic cells. LL-37 was also found to be located in CD1a-expressing Langerhans cells and a positive staining for the peptide was seen throughout the whole epidermal layer, both in infants with and without the rash. Skin samples from infants with the rash of erythema toxicum showed a constitutive expression of human beta defensin-1, while the expression of LL-37 seemed to be induced. Furthermore, LL-37 and lysozyme were detected in the protein fractions derived from the vernix caseosa, and these fractions exhibited a clear antibacterial activity.

CONCLUSIONS

Peptide antibiotics are present in the vernix caseosa and in the skin of the healthy newborn infant, indicating effective innate immune protection already during fetal and neonatal life.

摘要

背景

肽类抗生素是抵御微生物入侵者的体表防御机制的一部分。然而,这些先天性免疫效应分子在新生儿皮肤屏障中的存在及意义尚未得到充分认识。新生儿毒性红斑是一种病因和意义不明的炎症性皮肤反应,常见于健康新生儿。

目的

由于肽类抗生素在炎症性皮肤病中表达上调,我们推测新生儿毒性红斑可能也是如此。我们还研究了出生时婴儿皮肤上存在的白色奶油状物质胎脂是否有助于宿主防御。

方法

通过免疫组织化学和共聚焦成像,对4例患有新生儿毒性红斑皮疹的1日龄婴儿和4例匹配的无皮疹新生儿的皮肤活检组织进行人抗菌肽LL-37检测。此外,我们通过逆转录聚合酶链反应分析了LL-37和人β-防御素-1(一种上皮来源的抗菌肽)的表达。最后,我们通过抑菌圈试验筛选了6例健康新生儿的胎脂中的抗菌成分。

结果

所有新生儿毒性红斑皮损的活检组织均显示密集的结节状浸润,真皮层有大量表达LL-37的细胞,该肽在表达CD15 的中性粒细胞、表达EG2 的嗜酸性粒细胞和表达CD1a 的树突状细胞中有明确的定位。还发现LL-37存在于表达CD1a 的朗格汉斯细胞中,无论有无皮疹的婴儿,整个表皮层均可见该肽的阳性染色。患有新生儿毒性红斑皮疹的婴儿的皮肤样本显示人β-防御素-1的组成性表达,而LL-37的表达似乎是诱导性的。此外,在胎脂的蛋白质组分中检测到LL-37和溶菌酶,这些组分表现出明显的抗菌活性。

结论

肽类抗生素存在于胎脂和健康新生儿的皮肤中,表明在胎儿期和新生儿期就已经有有效的先天性免疫保护。

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