title: Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells.
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.
authors.affiliation: Basic Research Program, SAIC-Frederick, Laboratory of Molecular Regulation, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg 560, Rm 31-19, Frederick, MD 21702-1201, USA. dyang@mail.ncifcrf.gov
authors.forename: De
authors.initials: D
authors.lastname: Yang
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.forename: Kahori
authors.initials: K
authors.lastname: Kurosaka
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oppenheim
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D000998:Antiviral Agents / Q000494:pharmacology / Q000502:physiology*; D051836:COUP Transcription Factors; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D047208:Eosinophil-Derived Neurotoxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D006801:Humans; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D012260:Ribonucleases / Q000494:pharmacology / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; D000998:Antiviral Agents; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; C484221:Nr2f6 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C479821:Ear2 protein, mouse; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; C479221:RNASE2 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go