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

B Becknell, TE Eichler, S Beceiro, B Li, RS Easterling… - Kidney international, 2015 - Elsevier
B Becknell, TE Eichler, S Beceiro, B Li, RS Easterling, AR Carpenter, CL James…
Kidney international, 2015Elsevier
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 …
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.
Elsevier