Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract

  • Kidney Int. 2015 Jan;87(1):151-61. doi: 10.1038/ki.2014.268.
Brian Becknell  1 ,  Tad E Eichler  2 ,  Susana Beceiro  3 ,  Birong Li  2 ,  Robert S Easterling  2 ,  Ashley R Carpenter  4 ,  Cindy L James  5 ,  Kirk M McHugh  6 ,  David S Hains  7 ,  Santiago Partida-Sanchez  3 ,  John D Spencer  1
Affiliations
  • 1. 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.
  • 2. Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
  • 3. Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
  • 4. Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, USA.
  • 5. Mass Spec and Proteomic Facility, The Ohio State University, Columbus, Ohio, USA.
  • 6. 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.
  • 7. Department of Pediatrics, Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
PMID: 25075772 DOI: 10.1038/ki.2014.268
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.