title: Eosinophil-associated ribonuclease 11 is a macrophage chemoattractant.
abstract: RNase A is the prototype of an extensive family of divergent proteins whose members share a unique disulfide-bonded tertiary structure, conserved catalytic motifs, and the ability to hydrolyze polymeric RNA. Several members of this family maintain independent roles as ribonucleases and modulators of innate immunity. Here we characterize mouse eosinophil-associated RNase (Ear) 11, a divergent member of the eosinophil ribonuclease cluster, and the only known RNase A ribonuclease expressed specifically in response to Th2 cytokine stimulation. Mouse Ear 11 is differentially expressed in somatic tissues at baseline (brain ≪ liver < lung < spleen); systemic stimulation with IL-33 results in 10-5000-fold increased expression in lung and spleen, respectively. Ear 11 is also expressed in response to protective priming of the respiratory mucosa with Lactobacillus plantarum; transcripts are detected both locally in lung as well as systemically in bone marrow and spleen. Mouse Ear 11 is enzymatically active, although substantially less so than mEar 1 and mEar 2; the relative catalytic efficiency (kcat/Km) of mEar 11 is diminished ∼1000-1500-fold. However, in contrast to RNase 2/EDN and mEar 2, which have been characterized as selective chemoattractants for CD11c(+) dendritic cells, mEar 11 has prominent chemoattractant activity for F4/80(+)CD11c(-) tissue macrophages. Chemoattractant activity is not dependent on full enzymatic activity, and requires no interaction with the pattern recognition receptor, Toll-like receptor 2 (TLR2). Taken together, this work characterizes a divergent RNase A ribonuclease with a unique expression pattern and function, and highlights the versatility of this family in promoting innate immunity.
authors.affiliation: From the Inflammation Immunobiology and.
authors.forename: Kelsey J
authors.initials: KJ
authors.lastname: Yamada
authors.affiliation: Molecular Signal Transduction Sections, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Tolga
authors.initials: T
authors.lastname: Barker
authors.affiliation: From the Inflammation Immunobiology and.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.affiliation: From the Inflammation Immunobiology and.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Rice
authors.affiliation: From the Inflammation Immunobiology and.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Percopo
authors.affiliation: From the Inflammation Immunobiology and.
authors.forename: Katia E
authors.initials: KE
authors.lastname: Garcia-Crespo
authors.affiliation: the Department of Biology, Creighton University, Omaha, Nebraska 68178, and.
authors.forename: Soochin
authors.initials: S
authors.lastname: Cho
authors.affiliation: the Department of Biochemistry and Molecular Biology, Division of Pulmonary Medicine, Mayo Clinic, Scottsdale, Arizona 85259.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Molecular Signal Transduction Sections, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Druey
authors.affiliation: From the Inflammation Immunobiology and hrosenberg@niaid.nih.gov.
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D047150:Eosinophil Cationic Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000166:cytology
chemical_list: D017931:DNA Primers; D047150:Eosinophil Cationic Protein
keywords: Eosinophil; Evolution; Macrophage; Ribonuclease; Toll-like receptor (TLR)