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

β-Defensins are antibiotic peptides involved in host defense at the epithelial surface. Three human β-defensins (hBDs)--hBD-1, hBD-2, and hBD-3--have been identified so far. We have characterized a new member of the β-defensin family, hBD-4, based on screening of genomic sequences and subsequent functional analysis. In contrast to hBD-1, hBD-2, and hBD-3, which are diffusely expressed throughout many organs, hBD-4 mRNA expression is confined to testis, stomach, uterus, neutrophils, thyroid, lung, and kidney. hBD-4 expression was up-regulated by infection with gram-positive and gram-negative bacteria in human respiratory epithelial cells, and in response to phorbol 12-myristate 13-acetate, but not in response to other inflammatory factors that up-regulate the expression of hBD-2 or hBD-3. Synthetic hBD-4 exhibits a selective, salt-sensitive spectrum of antimicrobial activity, and it represents one of the most active antimicrobial peptides against Pseudomonas aeruginosa (minimal inhibitory concentration: 4.1 μg/ml) known to date. This new defensin is chemotactic for human blood monocytes, but it is inactive on neutrophils and eosinophils. These findings demonstrate the existence of a family of β-defensin genes with different functions against diverse classes of microorganisms, regulated by different stimuli, and specific signal pathways, and confirm the relevance of antimicrobial peptides in host defense.