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Research Article

Regulation of Extracellular Chromatin Release from Neutrophils

Neeli I. · Dwivedi N. · Khan S. · Radic M.

Author affiliations

Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tenn., USA

Corresponding Author

Dr. Marko Radic

Department of Molecular Sciences

University of Tennessee Health Science Center

858 Madison Avenue, Room 211, Memphis, TN 38163 (USA)

Tel. +1 901 448 8219, Fax +1 901 448 8462, E-Mail mradic@utmem.edu

Related Articles for ""

J Innate Immun 2009;1:194–201

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Neutrophils use intricate mechanisms for capturing and killing invading microorganisms. One mechanism entails the release of relaxed chromatin from the cell. Microbes are trapped by the extracellular chromatin and exposed to high local concentrations of bactericidal compounds. We examine the regulation of chromatin release by testing the contribution of microtubules and the actin cytoskeleton to the deployment of neutrophil extracellular traps (NETs). Incubation of human neutrophils with nocodazole, a tubulin polymerization inhibitor, or cytochalasin D, an inhibitor of actin filamentation, severely diminished the ability of neutrophils to respond to LPS by releasing chromatin from the cells. In addition, pretreatment of neutrophils with M1/70, a monoclonal antibody to the Mac-1 integrin adhesion receptor, drastically reduced the deployment of chromatin into NETs. Analysis of histone deimination, the conversion of arginine to citrulline in 3 of the 4 core histones by peptidylarginine deiminase 4, revealed that the treatments inhibiting NET formation also reduced histone deimination. Our data indicate that NET formation requires functional tubulin and actin filaments and responds to engagement of Mac-1 integrins. Because histone deimination coincides with the release of NETs, we propose that these events represent overlapping mechanisms of neutrophil responses to infections.

© 2009 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: October 08, 2008
Accepted: November 05, 2008
Published online: February 27, 2009
Issue release date: April 2009

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 0

ISSN: 1662-811X (Print)
eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN

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