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.
Niedersächsisches Institut für Peptid-Forschung (IPF), Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany. hdz@compuserve.com
H D
HD
Zucht
J
J
Grabowsky
M
M
Schrader
C
C
Liepke
M
M
Jürgens
P
P
Schulz-Knappe
W G
WG
Forssmann
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D001483:Base Sequence; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D002455:Cell Division; D002478:Cells, Cultured; D017931:DNA Primers; D023082:Defensins; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D023083:beta-Defensins
D000890:Anti-Infective Agents; D001798:Blood Proteins; C406407:DEFB1 protein, human; D017931:DNA Primers; D023082:Defensins; D012333:RNA, Messenger; D023083:beta-Defensins; D010450:Endopeptidases