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      Bactericidal Activity of Renal Tubular Cells: The Putative Role of Human β-Defensins

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          Renal tubular epithelial cells (RTC) form a barrier between the host and ascending microbes in upper urinary tract infection. Previous studies have shown the ability of the kidney to produce defensins – antimicrobial peptides that play a pivotal role in unspecific host defense. To further clarify the role of renal epithelium for direct antibacterial activity we investigated the expression, regulation and production of antimicrobial peptides by cultured human RTC. Cell culture supernatants of RTC exert strong bactericidal activity against Escherichia coli and Klebsiella pneumoniae, two of the most important pathogens in urinary tract infections. The antimicrobial effect depends on salt concentration, a typical feature of human defensins. RT-PCR of RNA from cultured proximal and distal RTC showed constitutive expression of human β-defensin 1 (hbd-1) and human β-defensin 2 (hbd-2) whereas only hbd-1 expression could be detected in RNA preparation from renal biopsy material. Hbd-2 expression of RTC was induced by inflammatory processes as shown by semiquantitative competitive RT-PCR. Coincubation of the cultured cells with IL-1α or E. coli promote the strongest hbd-2 induction whereas TNF-α and LPS lead to a weaker or no (IL-6) hbd-2 induction. This is the first evidence that human RTC are able to produce antibacterial substances in a biologically relevant amount and that β-defensins are candidate proteins responsible for this effect.

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          Most cited references 7

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          Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic.

          The growing public health problem of infections caused by multiresistant Gram-positive bacteria, in particular Staphylococcus aureus, prompted us to screen human epithelia for endogenous S. aureus-killing factors. A novel 5-kDa, nonhemolytic antimicrobial peptide (human beta-defensin-3, hBD-3) was isolated from human lesional psoriatic scales and cloned from keratinocytes. hBD-3 demonstrated a salt-insensitive broad spectrum of potent antimicrobial activity against many potentially pathogenic microbes including multiresistant S. aureus and vancomycin-resistant Enterococcus faecium. Ultrastructural analyses of hBD-3-treated S. aureus revealed signs of cell wall perforation. Recombinant hBD-3 (expressed as a His-Tag-fusion protein in Escherichia coli) and chemically synthesized hBD-3 were indistinguishable from naturally occurring peptide with respect to their antimicrobial activity and biochemical properties. Investigation of different tissues revealed skin and tonsils to be major hBD-3 mRNA-expressing tissues. Molecular cloning and biochemical analyses of antimicrobial peptides in cell culture supernatants revealed keratinocytes and airway epithelial cells as cellular sources of hBD-3. Tumor necrosis factor alpha and contact with bacteria were found to induce hBD-3 mRNA expression. hBD-3 therefore might be important in the innate epithelial defense of infections by various microorganisms seen in skin and lung, such as cystic fibrosis.
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            A peptide antibiotic from human skin.

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              hBD-1: a novel β-defensin from human plasma


                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                09 October 2002
                : 10
                : 5-6
                : 332-337
                aDivision of Nephrology, Department of Internal Medicine I, Medical University of Lübeck and bDivision of Nephrology, Department of Internal Medicine IV, J.W. Goethe University, Frankfurt, Germany
                65296 Exp Nephrol 2002;10:332–337
                © 2002 S. Karger AG, Basel

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                Page count
                Figures: 5, References: 21, Pages: 6
                Self URI (application/pdf):
                Original Paper

                Cardiovascular Medicine, Nephrology

                Renal tubular cells, Antibacterial activity, Defensins


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