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 defe nse of the human body. The human beta -defensins 1 and 2 (hBD-1, hBD-2) hav e been isolated by biochemical methods. Here we report the identification o f a third human beta -defensin, called human beta -defensin 3 (hBD-3; cDNA sequence, Genbank accession no. AF295370), based on bioinformatics and func tional genomic analysis. Expression of hBD-3 is detected throughout epithel ia of many organs and in non-epithelial tissues. In contrast to hBD-2, whic h is upregulated by microorganisms or tumor necrosis factor-alpha (TNF-alph a), hBD-3 expression is increased particularly after stimulation by interfe ron-gamma. Synthetic hBD-3 exhibits a strong antimicrobial activity against gram-negative and grampositive bacteria and fungi, including Burkholderia cepacia. In addition, hBD-3 activates monocytes and elicits ion channel act ivity in biomembranes, specifically in oocytes of Xenopus laevis. This pape r also shows that screening of genomic sequences is a valuable tool with wh ich 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 no t only related to direct host defense.