| 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 |
Related Documents
:
|
22514467 - Plesiomonas shigelloides septicemia and meningitis in a neonate. 16333837 - Favorable histology, mycn-amplified 4s neonatal neuroblastoma. 20664187 - Prevalence of testicular adrenal rest tissue in neonates. 20339307 - Bednar's aphthae in neonates: incidence and associated factors. 339007 - Total anomalous pulmonary venous connection. long-term results following repair in infa... 626817 - The "mandibular mantle"--a sign of rickets in very low birth weight infants. |
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Human and murine amniotic fluid c-Kit+Lin- cells display hematopoietic activity.
Next Document: A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function.