Cathelicidins comprise a family of antimicrobial peptides sharing a highly conserved cathelin domain. Here we report that the entire chicken genome encodes three cathelicidins, namely fowlicidin-1 to -3, which are densely clustered within a 7.5-kb distance at the proximal end of chromosome 2p. Each fowlicidin gene adopts a fourexon, three-intron structure, typical for a mammalian cathelicidin. Phylogenetic analysis revealed that fowlicidins and a group of distantly related mammalian cathelicidins known as neutrophilic granule proteins are likely to originate from a common ancestral gene prior to the separation of birds from mammals, whereas other classic mammalian cathelicidins may have been duplicated from the primordial gene for neutrophilic granule proteins after mammals and birds are diverged. Similar to ovine cathelicidin SMAP-29, putatively mature fowlicidins displayed potent and salt-independent activities against a range of Gram-negative and Gram- Cationic antimicrobial peptides comprise a large group of gene-encoded molecules that have been discovered in virtually all species of life, playing a critical role in innate host defense and disease resistance (1-4). Two major families of antimicrobial peptides exist in mammals, namely defensins and cathelicidins. Whereas defensins are characterized by the presence of six cysteines at well defined positions (5, 6), all cathelicidins share a highly conserved "cathelin" pro-sequence at the N terminus, followed by diversified, cationic mature sequences at the C terminus (7-9). Cathelicidins are most abundantly present in the granules of phagocytic cells and also to a lesser extent in many other cell types such as mucosal epithelial cells and skin keratinocytes (7-9).Upon activation, most cathelicidin precursors are proteolytically cleaved to release the cathelin domain and the C-terminal mature peptides with antimicrobial activities, although the unprocessed or differentially processed forms are often found in the biological fluids where cathelicidins are expressed (8, 9). The physiological role of the cathelin domain or uncleaved precursors remains elusive but is more likely to be involved in immune modulation other than just bacterial killing (10, 11).In addition to their ability to directly kill a wide range of bacteria, fungi, and enveloped viruses, mature cathelicidins are actively involved in various phases of host defense. Certain cathelicidins are found to chemoattract and activate a variety of immune cells, inhibit NADPH oxidase, kill activated lymphocytes, and promote angiogenesis and wound healing (1,8,9). Consistent with their critical role in host defense and disease resistance, aberrant expression of cathelicidins is often associated with various disease processes. For example, LL-37/hCAP-18 deficiency correlates with recurrent skin infections in the atopic dermatitis patients (12) and chronic periodontal disease in morbus Kostmann patients (13). Similarly, deletion of the cathelicidin gene (CRAMP) in mice resulted in a loss of protection against sk...

Mammalian beta-defensins are an important family of innate host defense peptides with pleiotropic activities. As a first step to study the evolutionary relationship and biological role of the beta-defensin family, we identified their complete repertoires in the human, chimpanzee, mouse, rat, and dog following systemic, genome-wide computational searches. Although most beta-defensin genes are composed of two exons separated by an intron of variable length, some contain an additional one or two exons encoding an internal pro-sequence, a segment of carboxy-terminal mature sequences or untranslated regions. Alternatively, spliced isoforms have also been found with several beta-defensins. Furthermore, all beta-defensin genes are densely clustered in four to five syntenic chromosomal regions, with each cluster spanning <1.2 Mb across the five species. Phylogenetic analysis indicated that, although the majority of beta-defensins are evolutionarily conserved across species, subgroups of gene lineages exist that are specific in certain species, implying that some beta-defensins originated after divergence of these mammals from each other, while most others arose before the last common ancestor of mammals. Surprisingly, RT-PCR revealed that all but one rat beta-defensin transcript are preferentially expressed in the male reproductive tract, particularly in epididymis and testis, except that Defb4, a human beta-defensin-2 ortholog, is more restricted to the respiratory and upper gastrointestinal tracts. Moreover, most beta-defensins expressed in the reproductive tract are developmentally regulated, with enhanced expression during sexual maturation. Existence of such a vast array of beta-defensins in the male reproductive tract suggests that these genes may play a dual role in both fertility and host defense.