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Review
. 2015 Jul 8;16(7):15442-55.
doi: 10.3390/ijms160715442.

Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense

Helene F Rosenberg  1
Affiliations
Review

Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense

Helene F Rosenberg. Int J Mol Sci. .

Abstract

The eosinophil-derived neurotoxin (EDN/RNase2) and its divergent orthologs, the mouse eosinophil-associated RNases (mEars), are prominent secretory proteins of eosinophilic leukocytes and are all members of the larger family of RNase A-type ribonucleases. While EDN has broad antiviral activity, targeting RNA viruses via mechanisms that may require enzymatic activity, more recent studies have elucidated how these RNases may generate host defense via roles in promoting leukocyte activation, maturation, and chemotaxis. This review provides an update on recent discoveries, and highlights the versatility of this family in promoting innate immunity.

Keywords: chemoattractant; evolution; inflammation; leukocyte.

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Figures

Figure 1
Figure 1
Human and mouse eosinophils. (A) Human eosinophils from peripheral blood exhibit characteristic bilobed nuclei and large red-stained cytoplasmic secretory granules; (B) Eosinophils isolated from the spleen of an interleukin-5 transgenic mouse. Cells in panels (A,B) were stained with the modified Giemsa protocol. Cells with multi-lobed nuclei and without large granules are neutrophils; original magnification, 100×; (C) Transmission electron micrograph of a mouse eosinophil. Two of the cytoplasmic secretory granules are indicated by white arrows just to the left of the lower lobe of the nucleus. The central core of the eosinophil specific granule contains the cationic major basic protein (MBP). The remaining major cationic proteins, including EDN, ECP and EPX, as well as cytokines, chemokines, growth factors and enzymes are localized in the peripheral portion of the granule; original magnification 6000×. Reprinted from [1] with permission from Nature Publishing Group.
Figure 2
Figure 2
Ribbon diagram of the three-dimensional structure of human EDN. The relative positions of catalytic His 15, His 129, and Lys 38 are as shown, structure determined at 0.98 angstroms. Reprinted from [30] with permission from American Chemical Society.
Figure 3
Figure 3
Neighbor-joining tree documenting phylogenetic relationships among the mouse eosinophil-associated ribonuclease genes and pseudogenes. Sequences were aligned using ClustalW; the unrooted tree was created with MEGA 6.0 [47] with bootstrap values (5000 replicates) above 50 as shown.
Figure 4
Figure 4
Recombinant human EDN limits the infectivity of the human RSV pathogen for target respiratory epithelial cells in vitro. Human EDN displays dose-dependent antiviral activity that is abolished when the protein is rendered catalytically inactive (rhEDNdK38). Reprinted from [54] with permission from Oxford University Press.
Figure 5
Figure 5
Recombinant mEar2 promotes leukocyte recruitment in vivo. Recombinant mEar 2 (but not human angiogenin) elicited recruitment of CD11c+ dendritic cells as a fraction of total leukocytes into airpouches. Reprinted from [68] with permission from American Society of Hematology.
Figure 6
Figure 6
Recombinant P. pastoris-derived mEar 11 is chemoattractant for F4/80+CD11c− macrophages. (A) Chemotactic indices calculated for leukocyte subsets, including Ly6G+ (neutrophils), CD11c+F4/80− (dendritic cells) and F4/80+CD11c− (macrophages); * p < 0.05; (B) Representative flow plots documenting that F4/80+CD11c− splenocytes (within boxes) from TLR2−/− mice migrated in response to mEar 11 to an extent indistinguishable from those from wild-type mice. Reprinted from [73] with permission from American Society for Biochemistry and Molecular Biology.
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