Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: Innate immunity during development of the adaptive response

Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: Innate immunity during development of the adaptive response
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DOI:
10.1203/01.pdr.0000057205.64451.b7
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发表时间:
2003-04-01
期刊:
影响因子:
3.6
通讯作者:
Gallo, RL
Gallo, RL
中科院分区:
医学3区
文献类型:
--
作者:
Dorschner, RA;Lin, KH;Gallo, RL

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抗菌肽和蛋白质的表达是一种重要的先天性免疫防御机制,近期研究表明它对皮肤抵御侵袭性细菌疾病至关重要。新生儿的细胞免疫防御系统尚未成熟,这导致其对感染的易感性增加。在此我们发现,胚胎和新生小鼠的皮肤以及人类新生儿包皮都表达cathelicidin和β - 防御素基因家族的抗菌肽。免疫组织化学和原位杂交显示,在围产期正常皮肤中存在大量的cathelicidin蛋白和mRNA。实时定量PCR表明,小鼠cathelicidin的表达(CRAMP)在围产期比成年期高10到100倍。小鼠β - 防御素 - 1和 - 4以及人类β - 防御素 - 2也存在于新生儿皮肤中。综合来看,人类cathelicidin(LL - 37/hCAP/18)和β - 防御素 - 2表现出协同的抗菌活性,能有效杀灭B族链球菌,这是一种重要的新生儿病原体。因此,在新生儿期细胞免疫应答机制发育过程中,抗菌肽可能提供一种补偿性的先天性防御机制。
The expression of antimicrobial peptides and proteins is an important innate immune defense mechanism that has recently been shown to be essential for cutaneous defense against invasive bacterial disease. Newborns have an immature cellular immune defense system that leads to increased susceptibility to infections. Here we show that skin from embryonic and newborn mice, as well as human newborn foreskin, express antimicrobial peptides of the cathelicidin and beta-defensin gene families. Immunohistochemistry and in situ hybridization demonstrated abundant cathelicidin protein and mRNA is present in normal skin during the perinatal period. Quantitative real-time PCR showed mouse cathelicidin expression (CRAMP) is 10- to 100-fold greater in the perinatal period than adult. Murine beta-defensins-1 and -4 and human beta-defensin-2 were also present in newborn skin. Combined, human cathelicidin (LL-37/hCAP/18) and beta-defensin-2 demonstrated synergistic antimicrobial activity and efficiently killed group B Streptococcus, an important neonatal pathogen. Antimicrobial peptides may therefore provide a compensatory innate defense mechanism during development of cellular immune response mechanisms in the newborn period.