Expression and activity of beta-defensins and LL-37 in the developing human lung

Timothy D Starner; Birgitta Agerberth; Gudmundur H Gudmundsson; Paul B McCray Jr

doi:10.4049/jimmunol.174.3.1608

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Expression and activity of beta-defensins and LL-37 in the developing human lung

Journal article

Peer reviewed

Expression and activity of beta-defensins and LL-37 in the developing human lung

Timothy D Starner, Birgitta Agerberth, Gudmundur H Gudmundsson and Paul B McCray Jr

The Journal of immunology (1950), Vol.174(3), pp.1608-1615

02/01/2005

DOI: 10.4049/jimmunol.174.3.1608

PMID: 15661923

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Abstract

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 beta-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 beta-defensin in human neonatal lung. HBD-2 mRNA expression was developmentally regulated, induced by the proinflammatory factor IL-1beta, 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.

Fetus

Postpartum Period - immunology

Anti-Infective Agents - metabolism

Anti-Infective Agents - pharmacology

Humans

Antimicrobial Cationic Peptides - biosynthesis

Infant

Trachea - metabolism

Microbial Sensitivity Tests

RNA, Messenger - biosynthesis

Respiratory Mucosa - immunology

Lung - metabolism

Antimicrobial Cationic Peptides - genetics

Infant, Newborn

Organ Culture Techniques

Respiratory Mucosa - growth & development

Trachea - growth & development

beta-Defensins - genetics

Antimicrobial Cationic Peptides - pharmacology

Hypotonic Solutions

Saline Solution, Hypertonic

Interleukin-1 - pharmacology

Trachea - immunology

Adolescent

beta-Defensins - pharmacology

Lung - growth & development

Respiratory Mucosa - metabolism

Intubation, Intratracheal

beta-Defensins - biosynthesis

Lung - immunology

Details

Title: Subtitle: Expression and activity of beta-defensins and LL-37 in the developing human lung
Creators: Timothy D Starner - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA. timothy-starner@uiowa.edu
Birgitta Agerberth
Gudmundur H Gudmundsson
Paul B McCray Jr
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.174(3), pp.1608-1615
DOI: 10.4049/jimmunol.174.3.1608
PMID: 15661923
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: HL07638 / NHLBI NIH HHS HL61234 / NHLBI NIH HHS 2K12 HD27748 / NICHD NIH HHS HL67992 / NHLBI NIH HHS RR00059 / NCRR NIH HHS P30DK54759 / NIDDK NIH HHS
Language: English
Date published: 02/01/2005
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984093605602771

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