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

被引:109
作者
Marchini, G
Lindow, S
Brismar, H
Ståbi, B
Berggren, V
Ulfgren, AK
Lonne-Rahm, S
Agerberth, B
Gudmundsson, GH
机构
[1] Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden
[2] Karolinska Inst, Dept Rheumatol Res, Stockholm, Sweden
[3] Karolinska Inst, Dept Dermatol, Stockholm, Sweden
[4] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden
[5] Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden
关键词
antibiotics peptide; confocal microscopy; erythema toxicum; infant newborn; lysozyme; vernix caseosa;
D O I
10.1046/j.1365-2133.2002.05014.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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 0 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.
引用
收藏
页码:1127 / 1134
页数:8
相关论文
共 18 条
[1]   The human antimicrobial and chemotactic peptides LL-37 and α-defensins are expressed by specific lymphocyte and monocyte populations [J].
Agerberth, B ;
Charo, J ;
Werr, J ;
Olsson, B ;
Idali, F ;
Lindbom, L ;
Kiessling, R ;
Jörnvall, H ;
Wigzell, H ;
Gudmundsson, GH .
BLOOD, 2000, 96 (09) :3086-3093
[2]  
Baker Souad M., 1995, Indian Journal of Pediatrics, V62, P237, DOI 10.1007/BF02752334
[3]   The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface [J].
Bals, R ;
Wang, XR ;
Zasloff, M ;
Wilson, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (16) :9541-9546
[4]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[5]   ANTIBACTERIAL PEPTIDES - KEY COMPONENTS NEEDED IN IMMUNITY [J].
BOMAN, HG .
CELL, 1991, 65 (02) :205-207
[6]   HCAP-18, A CATHELIN/PRO-BACTENECIN-LIKE PROTEIN OF HUMAN NEUTROPHIL SPECIFIC GRANULES [J].
COWLAND, JB ;
JOHNSEN, AH ;
BORREGAARD, N .
FEBS LETTERS, 1995, 368 (01) :173-176
[7]   The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders [J].
Frohm, M ;
Agerberth, B ;
Ahangari, G ;
StahleBackdahl, M ;
Liden, S ;
Wigzell, H ;
Gudmundsson, GH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (24) :15258-15263
[8]   Expression of natural peptide antibiotics in human skin [J].
Fulton, C ;
Anderson, GM ;
Zasloff, M ;
Bull, R ;
Quinn, AG .
LANCET, 1997, 350 (9093) :1750-1751
[9]   Antibiotic peptides from higher eukaryotes: biology and applications [J].
Ganz, T ;
Lehrer, RI .
MOLECULAR MEDICINE TODAY, 1999, 5 (07) :292-297
[10]   Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis [J].
Goldman, MJ ;
Anderson, GM ;
Stolzenberg, ED ;
Kari, UP ;
Zasloff, M ;
Wilson, JM .
CELL, 1997, 88 (04) :553-560