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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-01-0151. This Article Full Text (PDF) All Versions of this Article: 2003-01-0151v1 102/9/3396    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 Yang, D. Articles by Oppenheim, J. J Search for Related Content PubMed PubMed Citation Articles by Yang, D. Articles by Oppenheim, J. J Social Bookmarking                   What's this? Submitted January 17, 2003 Accepted June 30, 2003 Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells De Yang*, Helene F Rosenberg, Qian Chen, Kimberly D Dyer, Kahori Kurosaka, and Joost J Oppenheim Center for Cancer Research at Frederick, National Cancer Institute, Frederick, MD, USA Eosinophil Pathophysiology Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA * Corresponding author; email: dyang{at}ncifcrf.gov. Recent publications have highlighted the chemotactic activities of antimicrobial proteins derived from the granules of neutrophils and basophils. Eosinophil granules also contain antimicrobial proteins. One of them is eosinophil-derived neurotoxin (EDN), a protein belonging to the ribonuclease (RNase) A superfamily, which has recently been found to have antiviral activity against respiratory syncytial virus and human immunodeficiency virus in vitro. By evaluating the effect of EDN on the migration of human leukocytes, we found that EDN was selectively chemotactic for dendritic cells (DCs). The DC chemotactic activity of EDN was inhibited by either pretreatment of DCs with pertussis toxin or by simultaneous addition of placental RNase inhibitor to inhibit the activity of EDN. The capacity of DCs to respond chemotactically to EDN was maintained even after maturation, and leukocytes other than DCs did not respond to EDN in this fashion. Screening a number of proteins belonging to the RNase A superfamily revealed that mouse eosinophil-associated RNase 2 (mEAR2), one of a cluster of divergent orthologs of human EDN, was also chemotactic for human as well as mouse DCs. Sequence and mutational analysis demonstrated the importance of the N-terminal region of mEAR2 in mediating its chemotactic effect on DCs. In addition to induction of chemotaxis, EDN also induced the activation of p42/44 MAPK in DCs. Furthermore, injection of mEAR2 into the air pouches of mice resulted in the recruitment of DCs into the air pouches. Thus, EDN and its mouse ortholog, mEAR2 are eosinophil granule-derived antimicrobial RNases that function as chemoattractants for DCs in vitro and in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Soehnlein and L. Lindbom Neutrophil-derived azurocidin alarms the immune system J. Leukoc. Biol., March 1, 2009; 85(3): 344 - 351. [Abstract] [Full Text] [PDF] H. F. Rosenberg RNase A ribonucleases and host defense: an evolving story J. Leukoc. Biol., May 1, 2008; 83(5): 1079 - 1087. [Abstract] [Full Text] [PDF] D. Yang, Q. Chen, S. B. Su, P. Zhang, K. Kurosaka, R. R. Caspi, S. M. Michalek, H. F. Rosenberg, N. Zhang, and J. J. Oppenheim Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses J. 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