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PMID:12855582

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Citation

Yang, D, Rosenberg, HF, Chen, Q, Dyer, KD, Kurosaka, K and Oppenheim, JJ (2003) Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells. Blood 102:3396-403

Abstract

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 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. 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 granule-derived antimicrobial RNases that function as chemoattractants for DCs in vitro and in vivo.

Links

PubMed Online version:10.1182/blood-2003-01-0151

Keywords

Animals; Antigens, CD34; Antiviral Agents/pharmacology; Antiviral Agents/physiology; COUP Transcription Factors; Chemotaxis, Leukocyte/drug effects; DNA-Binding Proteins/physiology; Dendritic Cells/cytology; Dendritic Cells/physiology; Dose-Response Relationship, Drug; Eosinophil-Derived Neurotoxin; GTP-Binding Protein alpha Subunits, Gi-Go; Humans; Mice; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases/drug effects; Mitogen-Activated Protein Kinases/metabolism; Monocytes/cytology; Receptors, Cytoplasmic and Nuclear; Ribonucleases/pharmacology; Ribonucleases/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ECP2

involved_in

GO:0006935: chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RNAS2

involved_in

GO:0006935: chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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