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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.
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Submitted July 30, 2007
Accepted December 24, 2007
Phagocytosis-independent antimicrobial activity of mast cells by means of extracellular trap formation
Maren von Kockritz-Blickwede, Oliver Goldmann, Pontus Thulin, Katja Heinemann, Anna Norrby-Teglund, Manfred Rohde, and Eva Medina*
Infection Immunology Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
Center for Infectious Medicine, Karolinska Institute, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Braunschweig, Germany
* Corresponding author; email: eva.medina{at}helmholtz-hzi.de.
Nowadays 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 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.

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