Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction.
Previous studies have shown the implication of beta-defensins in host defense of the human body. The human beta-defensins 1 and 2 (hBD-1, hBD-2) have been isolated by biochemical methods. Here we report the identification of a third human beta-defensin, called human beta-defensin 3 (hBD-3; cDNA sequence, Genbank accession no. AF295370), based on bioinformatics and functional genomic analysis. Expression of hBD-3 is detected throughout epithelia of many organs and in non-epithelial tissues. In contrast to hBD-2, which is upregulated by microorganisms or tumor necrosis factor-alpha (TNF-alpha), hBD-3 expression is increased particularly after stimulation by interferon-gamma. Synthetic hBD-3 exhibits a strong antimicrobial activity against gram-negative and gram-positive bacteria and fungi, including Burkholderia cepacia. In addition, hBD-3 activates monocytes and elicits ion channel activity in biomembranes, specifically in oocytes of Xenopus laevis. This paper also shows that screening of genomic sequences is a valuable tool with which to identify novel regulatory peptides. Human beta-defensins represent a family of antimicrobial peptides differentially expressed in most tissues, regulated by specific mechanisms, and exerting physiological functions not only related to direct host defense.
García
J R
JR
IPF Pharmaceuticals GmbH, Feodor-Lynen-Strasse 31, 30625 Hanover, Germany.
Jaumann
F
F
Schulz
S
S
Krause
A
A
Rodríguez-Jiménez
J
J
Forssmann
U
U
Adermann
K
K
Klüver
E
E
Vogelmeier
C
C
Becker
D
D
Hedrich
R
R
Forssmann
W G
WG
Bals
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016956:Burkholderia cepacia / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes; D018408:Patch-Clamp Techniques; D016415:Sequence Alignment; D014982:Xenopus laevis; D023083:beta-Defensins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; C422950:DEFB103A protein, human; D007473:Ion Channels; D023083:beta-Defensins