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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3396-3403.
Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-01-0151.
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PHAGOCYTES
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
From the Basic Research Program, SAIC-Frederick, MD; Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD; Eosinophil Pathophysiology Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
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 A (RNase A) superfamily, which has recently been found to have antiviral activity in vitro. 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. EDN was not chemotactic for leukocytes other than DCs. Mouse eosinophilassociated 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. EDN also induced the activation of p42/44 mitogen-activated protein kinase (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 granulederived antimicrobial RNases that function as chemoattractants for DCs in vitro and in vivo.

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