title: Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract.
abstract: Recent evidence suggests antimicrobial peptides protect the urinary tract from infection. Ribonuclease 7 (RNase 7), a member of the RNase A superfamily, is a potent epithelial-derived protein that maintains human urinary tract sterility. RNase 7 expression is restricted to primates, limiting evaluation of its antimicrobial activity in vivo. Here we identified ribonuclease 6 (RNase 6) as the RNase A superfamily member present in humans and mice that is most conserved at the amino acid level relative to RNase 7. Like RNase 7, recombinant human and murine RNase 6 has potent antimicrobial activity against uropathogens. Quantitative real-time PCR and immunoblot analysis indicate that RNase 6 mRNA and protein are upregulated in the human and murine urinary tract during infection. Immunostaining located RNase 6 to resident and infiltrating monocytes, macrophages, and neutrophils. Uropathogenic E. coli induces RNase 6 peptide expression in human CD14(+) monocytes and murine bone marrow-derived macrophages. Thus, RNase 6 is an inducible, myeloid-derived protein with markedly different expression from the epithelial-derived RNase 7 but with equally potent antimicrobial activity. Our studies suggest RNase 6 serves as an evolutionarily conserved antimicrobial peptide that participates in the maintenance of urinary tract sterility.
authors: 1] Division of Nephrology, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA [2] Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: Brian
authors: B
authors: Becknell
authors: Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: Tad E
authors: TE
authors: Eichler
authors: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: Susana
authors: S
authors: Beceiro
authors: Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: Birong
authors: B
authors: Li
authors: Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: Robert S
authors: RS
authors: Easterling
authors: Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, USA.
authors: Ashley R
authors: AR
authors: Carpenter
authors: Mass Spec and Proteomic Facility, The Ohio State University, Columbus, Ohio, USA.
authors: Cindy L
authors: CL
authors: James
authors: 1] Division of Anatomy, The Ohio State University College of Medicine, Columbus, Ohio, USA [2] Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: Kirk M
authors: KM
authors: McHugh
authors: Department of Pediatrics, Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
authors: David S
authors: DS
authors: Hains
authors: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: Santiago
authors: S
authors: Partida-Sanchez
authors: 1] Division of Nephrology, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA [2] Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: John D
authors: JD
authors: Spencer
mesh_terms: D000818:Animals; D004722:Endoribonucleases / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D012260:Ribonucleases / Q000502:physiology*; D014551:Urinary Tract / Q000201:enzymology* / Q000382:microbiology*
chemical_list: D004722:Endoribonucleases; C499501:RNase 6, mouse; D012260:Ribonucleases; C470000:Ribonuclease 7