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

ABSTRACT 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.