Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides

Antimicrobial peptides (AMPs) are an important component of the innate immune system playing a critical role in host defense and disease resistance in virtually all species of life [1-4]. AMPs generally consist of？<？100 amino acid residues, mostly cationic and amphipathic in nature, which allows them to bind and disrupt negatively charged microbial membranes leading to cell death. Because of non-specific physical interactions with membranes, it is extremely difficult for bacteria to develop resistance. In addition to being antimicrobial, a number of AMPs were recently found to exert a broad range of immunomodulatory roles by recruiting and activating all major types of innate and adaptive immune cells [3,5]. Therefore, AMPs are being actively developed for the control and prevention of infectious diseases, particularly against antibiotic-resistant bacteria [3].Cathelicidins are a major family of AMPs in vertebrate animals including chickens. All cathelicidins are synthesized as prepro-peptides, with the prepro-sequence being highly conserved across species and the carboxyl terminal, biologically active mature sequence highly diversified [6]. In mammals, besides the mucosal epithelial cells lining the digestive, respiratory, and reproductive tracts, cathelicidins are most abundantly expressed in myeloid progenitor cells and stored in neutrophil granules as pro-peptides, which are converted into active forms by proteolytic cleavage upon degranulation. The chicken genome was recently found to encode four genes for cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1 that span a 7.5-kb distance on chromosome 2 [7-10]. All four chicken cathelicidins are capable of killing a broad range of bacteria including antibiotic-resistant strains [9,11-14]. Like in mammals, fowlicidin-2/CMAP27 was shown to be localized in the granules of chicken heterophils, equivalent to mammalian neutrophils, and processed into a mature form upon stimulation with bacterial lipopolysacchar