Ribonuclease 7 is a potent antimicrobial peptide within the human urinary tract

Abstract

Although the urinary tract is constantly challenged by microbial invasion, it remains free from colonization. Although little is known about how the urinary tract maintains sterility, the presence of antimicrobial peptides (AMPs) in the urine suggests that they may play a role in its protection from infection. Ribonuclease 7 (RNase 7) is a potent AMP that was first identified in the skin. Here, we characterize the expression and relevance of RNase 7 in the human kidney and urinary tract. Using RNA isolated from healthy human tissue, we performed quantitative real-time PCR and found basal RNASE7 expression in kidney and bladder tissue. Immunohistochemical and immunofluorescent analysis localized RNase 7 to the urothelium of the bladder, ureter, and the intercalated cells of the collecting tubules. In control urine samples from healthy individuals, the concentration of RNase 7 was found to be in the low micromolar range; very abundant for an AMP. Antibacterial neutralization assays showed that urinary RNase 7 has potent antimicrobial properties against Gram-negative and Gram-positive uropathogenic bacteria. Thus, RNase 7 is expressed in the human kidney and urinary tract and it may have an important antimicrobial role in maintaining tract sterility.

Collecting Duct Intercalated Cell Function and Regulation

“…Urinary tract and kidney epithelial cells synthesize several AMPs, including defensins, cathelicidin, hepcidin, and ribonuclease 7 (RNAse7). Among these AMPs, defensins and RNAse7 are expressed in the kidney collecting duct (175). Defensins, which have broad-spectrum antimicrobial activity, are classified into two main subfamilies: a-and b-defensins.…”

Antimicrobial Peptides: New Frontiers in the Therapy of Infections

“…The finding that RNase 7 exhibited both antimicrobial and ribonuclease activity gave rise to the speculation that the enzymatic activity is involved in microbial killing. However, although the mechanisms involved in the antimicrobial properties of RNase 7 are not completely understood, its bactericidal activity has been linked to its capacity to permeate and disrupt the bacterial membrane, independent of its RNase activity (Spencer, 2011). RNase 7 is currently considered a major component of the antimicrobial protein and peptide group that constitutes the biochemical skin barrier (Boix & Nogués, 2007), being active in the low micromolar concentration range against S. aureus, P. aeruginosa, Propionibacterium acnes, and C. albicans (Spencer, 2011).…”

“…However, although the mechanisms involved in the antimicrobial properties of RNase 7 are not completely understood, its bactericidal activity has been linked to its capacity to permeate and disrupt the bacterial membrane, independent of its RNase activity (Spencer, 2011). RNase 7 is currently considered a major component of the antimicrobial protein and peptide group that constitutes the biochemical skin barrier (Boix & Nogués, 2007), being active in the low micromolar concentration range against S. aureus, P. aeruginosa, Propionibacterium acnes, and C. albicans (Spencer, 2011). The hypothesis that RNase 7 may play an important role in the cutaneous antimicrobial defense system is further supported by the observation that contact of keratinocytes with bacteria induces RNase 7 gene expression, a finding that is in agreement with what is known for other epithelial antimicrobial proteins like the human defensins hBD-2, hBD-3, and hBD-4.…”

Carbonic anhydrase 2 deficiency leads to increased pyelonephritis susceptibility

“…Escalating evidence shows that IC function as innate immunity effectors in addition to their traditional role in the maintenance of acid-base homeostasis. We (42) have previously characterized ribonuclease 7, a potent antimicrobial peptide with a broad range of activity against uropathogens in the human kidney. Renal ribonuclease 7 expression is limited to ICs, constitutively expressed at baseline, upregulated in response to infection, and secreted into the urine (42,43).…”

“…We (42) have previously characterized ribonuclease 7, a potent antimicrobial peptide with a broad range of activity against uropathogens in the human kidney. Renal ribonuclease 7 expression is limited to ICs, constitutively expressed at baseline, upregulated in response to infection, and secreted into the urine (42,43). ICs have been demonstrated to express other innate immune proteins, including neutrophil gelatinase-associated lipocalin, also known as lipocalin 2 (gene: Lcn2; protein: Ngal), IL-18 (gene: Il18), and human ␣-defensin 5 (15,28,41).…”