Journal article
Human beta-defensin-1: an antimicrobial peptide of urogenital tissues
The Journal of clinical investigation, Vol.101(8), pp.1633-1642
04/15/1998
DOI: 10.1172/JCI1861
PMCID: PMC508744
PMID: 9541493
Abstract
Antimicrobial peptides are widely distributed mediators of innate host defense in animals and plants. A 36 amino acid antimicrobial peptide belonging to the defensin family, and named human beta-defensin-1 (HBD-1), was purified recently from hemodialysate fluid, but its tissue sources were not identified. By Northern blotting, we found the highest concentrations of HBD-1 mRNA in the kidney and the female reproductive tract. In situ hybridization localized the HBD-1 mRNA in the epithelial layers of the loops of Henle, distal tubules, and the collecting ducts of the kidney and the epithelial layers of the vagina, ectocervix, endocervix, uterus, and fallopian tubes in the female reproductive tract. Using a novel technique designed to detect cationic peptides in urine, we recovered several forms of HBD-1 ranging in length from 36 to 47 amino acid (aa) residues and differing from each other by amino terminal truncation. The total concentration of HBD-1 forms in voided urine was estimated at 10-100 microg/liter, with individual variations in the total amount of HBD-1 peptides and the relative proportion of HBD-1 forms. Multiple forms of HBD-1 (size 36-47 aa) were also found in the blood plasma, bound to carrier macromolecules that released the peptide under acid conditions, and in vaginal mucosal secretions (39, 40, and 44 aa). By immunostaining, HBD-1 was located in the kidney within the lumen of the loops of Henle, but no intracellular storage sites were identified in renal or female reproductive tissues. Recombinant HBD-1 forms (36, 39, and 42 aa) and natural HBD-1 forms were antimicrobial to laboratory and clinical strains of Escherichia coli at micromolar concentrations. HBD-1 activity was not changed appreciably by low pH, but was inhibited by high salt conditions. Some of the HBD-1 peptides retained their activity against E. coli in unconcentrated (low conductance) urine, and the 36 aa form was microbicidal even in normal (high conductance) urine. Production of HBD-1 in the urogenital tract could contribute to local antimicrobial defense.
Details
- Title: Subtitle
- Human beta-defensin-1: an antimicrobial peptide of urogenital tissues
- Creators
- E V Valore - Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California 90095, USAC H Park - Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California 90095, USAA J Quayle - Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California 90095, USAK R Wiles - Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California 90095, USAP B McCray - Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California 90095, USAT Ganz - Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California 90095, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.101(8), pp.1633-1642
- DOI
- 10.1172/JCI1861
- PMID
- 9541493
- PMCID
- PMC508744
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 04/15/1998
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093367102771
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