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

Marchini, Giovanna; Lindow, S. W.; Brismar, Hjalmar; Ståbi, Berit; Berggren, V; Ulfgren, A-K; Lonne-Rahm, Sol-Britt; Agerberth, Birgitta; Guðmundsson, Guðmundur H.

doi:10.1046/j.1365-2133.2002.05014.x

Cited by 146 publications

(100 citation statements)

References 19 publications

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“…Furthermore, the concentrations of LL-37 at which we observed these effects were consistent with those observed in vivo during inflammation (21)(22)(23), probably produced predominantly by neutrophils and epithelial cells (16,19,22). Although LL-37 expression has also been reported in Langerhans cells, which might also contribute (24), no LL-37 expression was evident at the protein or RNA level in monocyte-derived DC in the immature or mature state (data not shown). It seems likely that this can be attributed to differences between Langerhans cells and monocyte-derived DC, and the cellular milieu.…”

Section: Discussionsupporting

confidence: 69%

“…Expression is significantly up-regulated in the inflamed skin (22), with a median concentration of 304 M (ϳ1.5 mg/ml) in skin lesions from patients with psoriasis (23) and increased by 2-to 3-fold in bronchoalveolar lavage fluid from infants with either systemic or pulmonary inflammation (21). Expression of LL-37 has also been reported in the Langerhans cells of infants with erythema toxicum (24). In addition to its antimicrobial and antiendotoxic activities, it has been reported to be chemotactic for monocytes, T lymphocytes, neutrophils, and mast cells (25,26), and capable of modulating the expression profile of chemokines, chemokine receptors, and additional genes in macrophages and other mammalian cells (27).…”

Section: Endritic Cells (Dc)mentioning

confidence: 92%

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The Cationic Antimicrobial Peptide LL-37 Modulates Dendritic Cell Differentiation and Dendritic Cell-Induced T Cell Polarization

Davidson

Currie

Reid

et al. 2004

The Journal of Immunology

374

222

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Dendritic cells (DC) are instrumental in orchestrating an appropriately polarized Th cell response to pathogens. DC exhibit considerable phenotypic and functional plasticity, influenced by lineage, Ag engagement, and the environment in which they develop and mature. In this study, we identify the human cationic peptide LL-37, found in abundance at sites of inflammation, as a potent modifier of DC differentiation, bridging innate and adaptive immune responses. LL-37-derived DC displayed significantly up-regulated endocytic capacity, modified phagocytic receptor expression and function, up-regulated costimulatory molecule expression, enhanced secretion of Th-1 inducing cytokines, and promoted Th1 responses in vitro. LL-37 may be an attractive therapeutic candidate for manipulating T cell polarization by DC.

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Endritic Cells (Dc)mentioning

confidence: 92%

The Cationic Antimicrobial Peptide LL-37 Modulates Dendritic Cell Differentiation and Dendritic Cell-Induced T Cell Polarization

Davidson

Currie

Reid

et al. 2004

The Journal of Immunology

374

222

View full text Add to dashboard Cite

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“…6 In contrast, it was possible that retention of a highly hydrated biological material such as vernix would impair temperature control due to increased evaporative heat loss. 7 The identification of antimicrobial constituents in vernix [8][9][10][11] supports the intriguing hypothesis that vernix may function prenatally to protect the fetus from acute or subacute chorioamnionitis and facilitate colonization of the skin with microorganisms after birth. Newborn infants undergo a progressive adaptation immediately after birth, including a slow reduction in surface hydration, decrease in skin pH, and SC dehydration/ desquamation with formation of a dry skin surface.…”

Section: Introductionmentioning

confidence: 88%

Vernix Caseosa in Neonatal Adaptation

Visscher¹,

Narendran²,

Pickens³

et al. 2005

J Perinatol

135

116

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OBJECTIVES:To characterize vernix caseosa in newborn infants with respect to factors that influence vernix distribution on the skin surface, vernix effects on thermal stability, skin hydration, acid mantle development, and vernix antioxidant properties. STUDY DESIGN:Vernix distribution was determined for 430 infants. Thermal stability was assessed in parallel groups following vernix retention (n ¼ 66) and removal (n ¼ 64). The effects of vernix retention on skin hydration, pH, erythema, and dryness/scaling were determined. Samples were analyzed for vitamin E before and after UV exposure. RESULTS:Vernix distribution depended upon gestational age, delivery mode, gender, race, and meconium exposure. Retention had no effect on axillary temperatures. Skin hydration was significantly higher for vernix-retained skin. Skin pH and erythema were significantly lower with retention. Vitamin E levels were decreased by ultraviolet radiation. CONCLUSIONS:Vernix is a naturally occurring barrier cream with multiple salubrious effects, which support its retention on the skin surface at birth.

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“…Components of the innate immune repertoire of airway epithelia include human ␤-defensins (HBDs) (7,8) and the only known human cathelicidin, LL-37 (9,10). Defensins and LL-37 are also present in the skin and vernix and contribute to the innate immunity of neonates (11,12). Recently, HBDs and LL-37 were shown to be increased in neonatal tracheal aspirates during infections (13); however, little is known about the development or regulation of human ␤-defensins and cathelicidins in neonatal lung.…”

mentioning

confidence: 99%

Expression and Activity of β-Defensins and LL-37 in the Developing Human Lung

Starner

Agerberth

Guðmundsson

et al. 2005

The Journal of Immunology

111

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Immaturity of innate immunity contributes to the increased susceptibility of human neonates to infection. The lung is a major portal of entry for potential pathogens in the neonate, and human β-defensins (HBDs) and LL-37 participate in pulmonary innate immunity. We hypothesized that these antimicrobial factors would be developmentally regulated, expressed by neonatal pulmonary tissues, and participate in neonatal innate immunity. We found HBD-2 to be the predominant β-defensin in human neonatal lung. HBD-2 mRNA expression was developmentally regulated, induced by the proinflammatory factor IL-1β, and decreased by dexamethasone. Additionally, HBD-2 abundance in neonatal tracheal aspirates increased as a function of gestational age. HBD-1 had a lower level of expression compared with HBD-2 and was induced by dexamethasone. HBD-3 and LL-37 messages were not detected in airway epithelial cultures. Additionally, each antimicrobial peptide exhibited a unique spectrum of antimicrobial activity and salt sensitivity against bacteria commonly causing sepsis in the neonate. Lower levels of HBD-2 may be one factor contributing to the increased susceptibility of premature infants to pulmonary infections.

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

Abstract: 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.

Cited by 146 publications

References 19 publications

The Cationic Antimicrobial Peptide LL-37 Modulates Dendritic Cell Differentiation and Dendritic Cell-Induced T Cell Polarization

The Cationic Antimicrobial Peptide LL-37 Modulates Dendritic Cell Differentiation and Dendritic Cell-Induced T Cell Polarization

Vernix Caseosa in Neonatal Adaptation

Expression and Activity of β-Defensins and LL-37 in the Developing Human Lung

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