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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6419-6427. Prepublished online as a Blood First Edition Paper on February 12, 2009; DOI 10.1182/blood-2008-07-171629. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-07-171629v1 113/25/6419    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yost, C. C. Articles by Zimmerman, G. A. Search for Related Content PubMed PubMed Citation Articles by Yost, C. C. Articles by Zimmerman, G. A. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 31, 2008 Accepted January 23, 2009 Impaired neutrophil extracellular trap (NET) formation: A novel innate immune deficiency of human neonates 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, and Guy A. Zimmerman Department of Pediatrics/Neonatology, University of Utah, Salt Lake City, UT, United States Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT, United States Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States Electron Microscopy Core Research Facility, University of Utah, Salt Lake City, UT, United States Cell Imaging/Fluorescence Microscopy Core Research Facility, University of Utah, Salt Lake City, UT, United States Department of Pathology, University of Utah, Salt Lake City, UT, United States * Corresponding author; email: christian.yost{at}hmbg.utah.edu. 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 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 ROS did not complement the defect in NET formation by neonatal neutrophils, as it did in adult cells with inactivated NADPH oxidase, demonstrating that ROS 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Delayed but functional neutrophil extracellular trap formation in neonates Veronica Marcos, Claudia Nussbaum, Ljubomir Vitkov, Andreas Hector, Eva-Maria Wiedenbauer, Dirk Roos, Taco Kuijpers, Wolf Dietrich Krautgartner, Orsolya Genzel-Boroviczény, Markus Sperandio, and Dominik Hartl Blood 2009 114: 4908-4911. [Full Text] [PDF] Response: Gestational age as a factor in neutrophil extracellular trap formation Christian Con Yost and Guy A. Zimmerman Blood 2009 114: 4911-4912. [Full Text] [PDF] Babies born without safety NET Bengt Fadeel Blood 2009 113: 6270-6271. [Abstract] [Full Text] [PDF] This article has been cited by other articles: V. Marcos, C. Nussbaum, L. Vitkov, A. Hector, E.-M. Wiedenbauer, D. Roos, T. Kuijpers, W. D. Krautgartner, O. Genzel-Boroviczeny, M. Sperandio, et al. Delayed but functional neutrophil extracellular trap formation in neonates Blood, November 26, 2009; 114(23): 4908 - 4911. [Full Text] [PDF] C. C. Yost and G. A. Zimmerman Response: Gestational age as a factor in neutrophil extracellular trap formation Blood, November 26, 2009; 114(23): 4911 - 4912. [Full Text] [PDF] R. A. Roberts, D. L. Laskin, C. V. Smith, F. M. Robertson, E. M. G. Allen, J. A. Doorn, and W. Slikker Nitrative and Oxidative Stress in Toxicology and Disease Toxicol. Sci., November 1, 2009; 112(1): 4 - 16. [Abstract] [Full Text] [PDF] B. Fadeel Babies born without safety NET Blood, June 18, 2009; 113(25): 6270 - 6271. [Abstract] [Full Text] [PDF]

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