Neutrophils play a critical role as a first line of defense against invading pathogens. Recently, a new defense strategy of neutrophils was described, in which pathogens are trapped and killed by NETs. However, the exact underlying mechanisms leading to the formation of NETs remain elusive. Here, we explored the role of the Rac small GTPases in the formation of NETs using neutrophils that lack Rac1, Rac2, or both isoforms. Efficient NET formation was observed in WT and Rac1null neutrophils. In contrast, NET formation was markedly impaired in cells lacking Rac2 or both Rac2 and Rac1. The defect in NET formation in Rac2null cells was rescued by exogenous ROS sources, suggesting that Rac2-mediated ROS generation is required for NET formation. In addition, we assessed the role of NO in NET formation in mouse neutrophils. Blocking NO production with the NOS inhibitor L-NAME significantly reduced NET formation. Moreover, we show that Rac2null cells produce significantly less NO than Rac1null cells or their WT counterparts. Our data suggest that Rac2 is essential for NET formation via pathways involving ROS and NO. NET NADPH oxidase nitric oxide synthase small GTPase ROS NO Footnotes The online version of this paper, found at www.jleukbio.org , includes supplemental information. CGD chronic granulomatous disease DAF-2DA 4,5-diaminofluorescein diacetate DPI diphenyleneiodonium GO glucose oxidase NAC N-acetyl-L-cysteine NET neutrophil extracellular trap Trolox (±)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid Received October 6, 2010. Revision received June 2, 2011. Accepted June 9, 2011. © 2011 Society for Leukocyte Biology Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print June 28, 2011 , doi: 10.1189/jlb.1010549 October 2011 Journal of Leukocyte Biology vol. 90 no. 4 771-776 » Abstract Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: jlb.1010549v1 90/4/771 most recent Classifications Host Defense & Pathophysiology Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Lim, M. B. H. Articles by Glogauer, M. PubMed PubMed citation Articles by Lim, M. B. H. Articles by Glogauer, M. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue October 2011, 90 (4) From the Cover Editorials: Granulopoiesis versus monopoiesis: a consequence of transcription factors dancing with the right partners. Editorials: Developmental regulation of P-glycoprotein and HIV therapy: spare the thymus but spoil the child? Spotlight on Leading Edge Research: AP-1 protein induction during monopoiesis favors C/EBP: AP-1 heterodimers over C/EBP homodimerization and stimulates FosB transcription. Spotlight on Leading Edge Research: Developmental regulation of P-glycoprotein activity within thymocytes results in increased anti-HIV protease inhibitor activity. Reviews: Role of alloreactive KIR2DS1+ NK cells in haploidentical hematopoietic stem cell transplantation. Reviews: Dendritic cells in bacteria handling in the gut. Reviews: Metabolism, LXR/LXR ligands, and tumor immune escape. Reviews: Plasmacytoid dendritic cells and cancer. Reviews: TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes. Reviews: Maternal KIR and fetal HLA-C: a fine balance. Technical Advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation. Alert me to new issues of Journal of Leukocyte Biology About JLB Submit Manuscripts Instructions for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Advertising Press Room Copyright Permissions Feedback Join SLB SLB Annual Meeting Copyright © 2011 by the Society for Leukocyte Biology Print ISSN: 0741-5400 Online ISSN: 1938-3673 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23108860-1"); pageTracker._trackPageview();

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