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

被引:101
作者
Dorschner, RA
Lin, KH
Murakami, M
Gallo, RL
机构
[1] Univ Calif San Diego, Dept Med & Pediat, Div Dermatol, La Jolla, CA 92093 USA
[2] Vet Adm San Diego Healthcare Syst, San Diego, CA USA
关键词
D O I
10.1203/01.PDR.0000057205.64451.B7
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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.
引用
收藏
页码:566 / 572
页数:7
相关论文
共 35 条
[31]   β-defensins:: Linking innate and adaptive immunity through dendritic and T cell CCR6 [J].
Yang, D ;
Chertov, O ;
Bykovskaia, N ;
Chen, Q ;
Buffo, MJ ;
Shogan, J ;
Anderson, M ;
Schröder, JM ;
Wang, JM ;
Howard, OMZ ;
Oppenheim, JJ .
SCIENCE, 1999, 286 (5439) :525-528
[32]   LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells [J].
Yang, D ;
Chen, Q ;
Schmidt, AP ;
Anderson, GM ;
Wang, JM ;
Wooters, J ;
Oppenheim, JJ ;
Chertov, O .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :1069-1074
[33]   The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity [J].
Yang, D ;
Chertov, O ;
Oppenheim, JJ .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2001, 58 (07) :978-989
[34]   Cathelicidins, essential gene-encoded mammalian antibiotics [J].
Zaiou, M ;
Gallo, RL .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2002, 80 (09) :549-561
[35]   Antimicrobial peptides of multicellular organisms [J].
Zasloff, M .
NATURE, 2002, 415 (6870) :389-395