Hepcidin, a urinary antimicrobial peptide synthesized in the liver

Cysteine-rich antimicrobial peptides are abundant in animal and plant tissu es involved in host defense. In insects, most are synthesized in the fat bo dy, an organ analogous to the liver of vertebrates. From human urine, we ch aracterized a cysteine-rich peptide with three forms differing by amino-ter minal truncation, and we named it hepcidin (Hepc) because of its origin in the liver and its antimicrobial properties. Two predominant forms, Hepc20 a nd Hepc25, contained 20 and 25 amino acid residues with all 8 cysteines con nected by intramolecular disulfide bonds. Reverse translation and search of the data bases found homologous liver cDNAs in species from fish to human and a corresponding human genomic sequence on human chromosome 19. The full cDNA by 5' rapid amplification of cDNA ends was 0.4 kilobase pair, in agre ement with hepcidin mRNA size on Northern blots. The liver was the predomin ant site of mRNA expression. The encoded prepropeptide contains 84 amino ac ids, but only the 20-25-amino acid processed forms were found in urine. Hep cidins exhibited antifungal activity against Candida albicans, Aspergillus fumigatus, and Aspergillus niger and antibacterial activity against Escheri chia coli, Staphylococcus aureus, Staphylococcus epidermidis, and group B S treptococcus. Hepcidin may be a vertebrate counterpart of cysteine-rich ant imicrobial peptides produced in the fat body of insects.