Expression and activity of beta-defensins and LL-37 in the developing human lung.
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.
Starner
Timothy D
TD
Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA. timothy-starner@uiowa.edu
Agerberth
Birgitta
B
Gudmundsson
Gudmundur H
GH
McCray
Paul B
PB
D000293:Adolescent; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D005333:Fetus; D006801:Humans; D007038:Hypotonic Solutions; D007223:Infant; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000494:pharmacology; D007442:Intubation, Intratracheal; D008168:Lung / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009924:Organ Culture Techniques; D049590:Postpartum Period / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D012462:Saline Solution, Hypertonic; D014132:Trachea / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D054804:Cathelicidins
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D007038:Hypotonic Solutions; D007375:Interleukin-1; D012333:RNA, Messenger; D012462:Saline Solution, Hypertonic; D023083:beta-Defensins; D054804:Cathelicidins