Document Detail


Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates.
MedLine Citation:
PMID:  19221037     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neutrophils are highly specialized innate effector cells that have evolved for killing of pathogens. Human neonates have a common multifactorial syndrome of neutrophil dysfunction that is incompletely characterized and contributes to sepsis and other severe infectious complications. We identified a novel defect in the antibacterial defenses of neonates: inability to form neutrophil extracellular traps (NETs). NETs are lattices of extracellular DNA, chromatin, and antibacterial proteins that mediate extracellular killing of microorganisms and are thought to form via a unique death pathway signaled by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-generated reactive oxygen species (ROS). We found that neutrophils from term and preterm infants fail to form NETs when activated by inflammatory agonists-in contrast to leukocytes from healthy adults. The deficiency in NET formation is paralleled by a previously unrecognized deficit in extracellular bacterial killing. Generation of ROSs did not complement the defect in NET formation by neonatal neutrophils, as it did in adult cells with inactivated NADPH oxidase, demonstrating that ROSs are necessary but not sufficient signaling intermediaries and identifying a deficiency in linked or downstream pathways in neonatal leukocytes. Impaired NET formation may be a critical facet of a common developmental immunodeficiency that predisposes newborn infants to infection.
Authors:
Christian C Yost; Mark J Cody; Estelle S Harris; Nathan L Thornton; Alison M McInturff; Mark L Martinez; Nancy B Chandler; Christopher K Rodesch; Kurt H Albertine; Cathy A Petti; Andrew S Weyrich; Guy A Zimmerman
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-02-12
Journal Detail:
Title:  Blood     Volume:  113     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-22     Completed Date:  2009-07-20     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6419-27     Citation Subset:  AIM; IM    
Affiliation:
Department of Pediatrics/Neonatology, University of Utah, Salt Lake City, USA. christian.yost@hmbg.utah.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Aging / immunology
Blood Bactericidal Activity*
Chromatin / physiology
DNA / physiology
Disease Susceptibility
Extracellular Space
Fetal Blood / cytology,  immunology
Humans
Infant, Newborn / immunology*
Infant, Premature / immunology*
Infection / immunology
Lipopolysaccharides / pharmacology
Macromolecular Substances / immunology*
Neutrophils / drug effects,  immunology,  pathology*
Platelet Activating Factor / pharmacology
Platelet Membrane Glycoproteins / biosynthesis,  genetics
RNA, Messenger / biosynthesis
Receptors, G-Protein-Coupled / biosynthesis,  genetics
Respiratory Burst
Toll-Like Receptor 4 / biosynthesis,  genetics
Grant Support
ID/Acronym/Agency:
5R01 HL066277-07/HL/NHLBI NIH HHS; 5R37 HL044525-20/HL/NHLBI NIH HHS; K08 HD049699/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Chromatin; 0/Lipopolysaccharides; 0/Macromolecular Substances; 0/Platelet Activating Factor; 0/Platelet Membrane Glycoproteins; 0/RNA, Messenger; 0/Receptors, G-Protein-Coupled; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 0/lipopolysaccharide, Escherichia coli 0111 B4; 0/platelet activating factor receptor; 9007-49-2/DNA
Comments/Corrections
Comment In:
Blood. 2009 Nov 26;114(23):4908-11; author reply 4911-2   [PMID:  19965699 ]
Blood. 2009 Jun 18;113(25):6270-1   [PMID:  19541833 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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