Eosinophil-associated Ribonuclease 11 Is a Macrophage Chemoattractant

• Published in: The Journal of biological chemistry Vol. 290; no. 14; pp. 8863 - 8875
• Main Authors: Yamada, Kelsey J., Barker, Tolga, Dyer, Kimberly D., Rice, Tyler A., Percopo, Caroline M., Garcia-Crespo, Katia E., Cho, Soochin, Lee, James J., Druey, Kirk M., Rosenberg, Helene F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.04.2015; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Base Sequence; DNA Primers; Eosinophil; Eosinophil Cationic Protein - chemistry; Eosinophil Cationic Protein - genetics; Eosinophil Cationic Protein - metabolism; Evolution; Immunity, Innate; Immunology; Macrophage; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Sequence Data; Phylogeny; Ribonuclease; Sequence Homology, Amino Acid; Spleen - cytology; Toll-like receptor (TLR); Evolution; Ribonuclease; Toll-like receptor (TLR); Eosinophil; Macrophage
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M114.626648

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. Background: The RNase A ribonucleases are enzymatically active secretory proteins that can promote innate immunity. Results: Mouse eosinophil-associated RNase (mEar) 11 is expressed in response to IL-33 and promotes TLR2-independent macrophage activation. Conclusion: Mouse Ear 11 is an RNase A ribonuclease with unique expression, targets, and functions. Significance: This work elucidates the versatility of RNase A ribonucleases in promoting innate immunity.