RNase 7, a Novel Innate Immune Defense Antimicrobial Protein of Healthy Human Skin

Abstract

We analyzed healthy human skin for the presence of endogenous antimicrobial proteins that might explain the unusually high resistance of human skin against infections. A novel 14.5-kDa antimicrobial ribonuclease, termed RNase 7, was isolated from skin-derived stratum corneum. RNase 7 exhibited potent ribonuclease activity and thus may contribute to the well known ribonuclease activity of human skin. RNase 7 revealed broad spectrum antimicrobial activity against many pathogenic microorganisms and remarkably potent activity (lethal dose of 90% < 30 nM) against a vancomycin-resistant Enterococcus faecium. Molecular cloning from skinderived primary keratinocytes and purification of RNase 7 from supernatants of cultured primary keratinocytes indicate that keratinocytes represent the major cellular source in skin and that RNase 7 is secreted. RNase 7 mRNA expression was detected in various epithelial tissues including skin, respiratory tract, genitourinary tract, and at a low level, in the gut. In addition to a constitutive expression, RNase 7 mRNA was induced in cultured primary keratinocytes by interleukin-1␤, interferon-␥, and bacterial challenge. This is the first report demonstrating RNases as a novel class of epithelial inducible antimicrobial proteins, which may play an important role in the innate immune defense system of human epithelia.

Outer Membrane Protein I of Pseudomonas aeruginosa Is a Target of Cationic Antimicrobial Peptide/Protein

“…In addition to the physical barrier of intact skin, the existence of a chemical barrier consisting of antimicrobial peptides/proteins (AMPs) 2 in a wide variety of organisms might contribute to the natural defense of skin against microbial infections (2)(3)(4). For example, secretion of defensins, psoriasin (S100A7), and hRNase 7 usually protects human skin against infection by most bacteria (5)(6)(7)(8).…”

“…As a member of the RNase A superfamily, hRNase 7 is a highly positively charged protein with 128 amino acids (6,9,10). It is abundant in healthy epithelial tissues, skin, and the respiratory tract and can be induced by interleukin 1␤, interferon ␥, and bacterial challenge in epithelial cell culture.…”

Peptidoglycan Recognition Proteins Are a New Class of Human Bactericidal Proteins

“…Besides forming a mechanical barrier, these tissues and their secretions are rich in antimicrobial peptides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), including defensins (1-6), phospholipase A 2 (7), dermicidin (8), cathelicidin (9), RNases (10), and psoriasin (11). Antimicrobial peptides are low molecular weight amphipathic molecules that kill microorganisms by damaging their membranes (1)(2)(3)(4).…”

Human ribonuclease 9, a member of ribonuclease A superfamily, specifically expressed in epididymis, is a novel sperm-binding protein

“…Except for these conserved residues, they exhibit diverse expression patterns and possess various catalytic activities against specific RNA substrates. They also exhibit a divergent physiological functions, including degradation of dietary RNA in the digestive gut (RNase 1) [6], angiogenesis (RNase 5) [7], and innate immunity (RNases 2, 3, 7) [8,9,10]. With the discovery of RNases-9, -10, -11, -12 and -13 [11][12][13], these requirements have been somewhat relaxed because these genes are clearly the derivatives of the RNase A lineage based on sequence similarity and the presence of the characteristic disulfide bridges, but they lack the active site signature motif and, as such, are unlikely to have ribonucleolytic activity.…”