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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3070-3080. Prepublished online as a Blood First Edition Paper on January 8, 2008; DOI 10.1182/blood-2007-07-104018. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-07-104018v1 111/6/3070    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 von Köckritz-Blickwede, M. Articles by Medina, E. Search for Related Content PubMed PubMed Citation Articles by von Köckritz-Blickwede, M. Articles by Medina, E. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Phagocytosis-independent antimicrobial activity of mast cells by means of extracellular trap formation Maren von Köckritz-Blickwede1, Oliver Goldmann1, Pontus Thulin2, Katja Heinemann1, Anna Norrby-Teglund2, Manfred Rohde3, and Eva Medina1 1 Infection Immunology Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany; 2 Center for Infectious Medicine, Karolinska Institute, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden; and 3 Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Braunschweig, Germany These days it has been increasingly recognized that mast cells (MCs) are critical components of host defense against pathogens. In this study, we have provided the first evidence that MCs can kill bacteria by entrapping them in extracellular structures similar to the extracellular traps described for neutrophils (NETs). We took advantage of the ability of MCs to kill the human pathogen Streptococcus pyogenes by a phagocytosis-independent mechanism in order to characterize the extracellular antimicrobial activity of MCs. Close contact of bacteria and MCs was required for full antimicrobial activity. Immunofluorescence and electron microscopy revealed that S pyogenes was entrapped by extracellular structures produced by MCs (MCETs), which are composed of DNA, histones, tryptase, and the antimicrobial peptide LL-37. Disruption of MCETs significantly reduced the antimicrobial effect of MCs, suggesting that intact extracellular webs are critical for effective inhibition of bacterial growth. Similar to NETs, production of MCETs was mediated by a reactive oxygen species (ROS)–dependent cell death mechanism accompanied by disruption of the nuclear envelope, which can be induced after stimulation of MCs with phorbol-12-myristate-13-acetate (PMA), H2O2, or bacterial pathogens. Our study provides the first experimental evidence of antimicrobial extracellular traps formation by an immune cell population other than neutrophils. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Di Nardo, K. Yamasaki, R. A. Dorschner, Y. Lai, and R. L. Gallo Mast Cell Cathelicidin Antimicrobial Peptide Prevents Invasive Group A Streptococcus Infection of the Skin J. Immunol., June 1, 2008; 180(11): 7565 - 7573. [Abstract] [Full Text] [PDF] F. Wartha and B. Henriques-Normark ETosis: A Novel Cell Death Pathway Sci. Signal., May 27, 2008; 1(21): pe25 - pe25. [Abstract] [Full Text] [PDF]

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