title: Eosinophils, ribonucleases and host defense: solving the puzzle.
abstract: The eosinophil ribonucleases eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3) are among the major secretory effector proteins of human eosinophilic leukocytes, cells whose role in host defense remains controversial and poorly understood. We have recently described the unusual manner in which this ribonuclease lineage has evolved, with extraordinary diversification observed in primate as well as in rodent EDNs and ECPs. The results of our evolutionary studies suggest that the EDN/ ECP ribonucleases are in the process of being tailored for a specific, ribonuclease-related goal. With this in mind, we have begun to look carefully at some of the intriguing associations that link eosinophils and their ribonucleases to disease caused by the single-stranded RNA viral pathogen, respiratory syncytial virus (RSV). Recent work in our laboratory has demonstrated that eosinophils can mediate a direct, ribonuclease-dependent reduction in infectivity of RSV in vitro, and that EDN can function alone as an independent antiviral agent. The results of this work have led us to consider the possibility that the EDN/ECP ribonucleases represent a heretofore unrecognized element of innate and specific antiviral host defense.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hr2k@nih.gov
authors.forename: H F
authors.initials: HF
authors.lastname: Rosenberg
authors.forename: J B
authors.initials: JB
authors.lastname: Domachowske
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D005075:Biological Evolution; D001798:Blood Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D047091:Eosinophil Granule Proteins; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000201:enzymology*; D006801:Humans; D007110:Immunity, Active / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects; D015183:Restriction Mapping; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D012260:Ribonucleases / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D016415:Sequence Alignment
chemical_list: D000998:Antiviral Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D011506:Proteins; D011994:Recombinant Proteins; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; D012259:Ribonuclease, Pancreatic