Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity

beta Defensins are antibiotic peptides involved in host defense at the epit helial surface. Three human beta -defensins (hBDs)-hBD-1, hBD-2, and hBD-3- have been identified so far. We have characterized a new member of the beta -defensin family, hBD-4, based on screening of genomic sequences and subse quent functional analysis. In contrast to hBD-1, hBD-2, and hBD-3, which ar e diffusely expressed throughout many organs, hBD-4 mRNA expression is conf ined to testis, stomach, uterus, neutrophils, thyroid, lung, and kidney. hB D-4 expression was up-regulated by infection with gram-positive and gram-ne gative bacteria in human respiratory epithelial cells, and in response to p horbol 12-myristate 13-acetate, but not in response to other inflammatory f actors that up-regulate the expression of hBD-2 or hBD-3. Synthetic hBD-4 e xhibits a selective, salt-sensitive spectrum of antimicrobial activity, and it represents one of the most active antimicrobial peptides against Pseudo monas aeruginosa (minimal inhibitory concentration: 4.1 mug/ml) known to da te. This new defensin is chemotactic for human blood monocytes, but it is i nactive on neutrophils and eosinophils. These findings demonstrate the exis tence of a family of beta -defensin genes with different functions against diverse classes of microorganisms, regulated by different stimuli, and spec ific signal pathways, and confirm the relevance of antimicrobial peptides i n host defense.