Human beta-defensin-1: A urinary peptide present in variant molecular forms and its putative functional implication.

Human beta-defensin-1 (hBD-1) was first isolated from blood filtrate by our group. Further studies elucidate the significance of this peptide in the human urogenital tract. The hBD-1 gene is expressed in urogenital epithelial organs such as urinary bladder, ureter, vagina and particularly in distal tubular cells of the kidney. Functional characterization of hBD-1 was carried out with native hBD-1 purified from human body fluids. Several different N-terminally truncated variants derived from the 68-amino acid-containing precursor of hBD-1 occur in blood filtrate and in urine. The generation of these variants can be explained by digestion through a chymotrypsin-like protease. Unlike the alpha-defensins which are structurally related peptide antibiotics, our results indicate that native hBD-1 exhibits minor antimicrobial activity which is not related to the extension of the N-terminus. Only few microorganisms, for example bacilli, are significantly inhibited by hBD-1. Moreover, antibiotic activity is suppressed in solutions containing physiological sodium chloride concentrations. This is in contrast to previous reports assuming a pivotal role of hBD-1 in antimicrobial host defense. In contrast to its weak antimicrobial activity, it is shown that hBD-1 has a strong cytotoxic potential towards mammalian cells like NIH-3T3 fibroblasts. We assume that this property might be important during eradicative processes at epithelia in particular when the synthesis rate of this peptide is upregulated.